To determine factors influencing compliance in patients with neovascular age-related macular degeneration (n-AMD) undergoing intravitreal anti-vascular endothelial growth factor (VEGF) therapy.The files of n-AMD patients recommended treatment with ranibizumab were reviewed retrospectively. The treatment regimen was 3 consecutive monthly injections followed by monthly follow-up with intravitreal injections as needed . Demographic and ocular characteristics were recorded. The patients were categorized into 2 groups: full compliance to treatment, or incomplete loading schedule and/or irregular maintenance treatment. All patients were interviewed by phone about factors affecting continuation of treatment.Mean age of the 314 patients  included in the study was 71.6±9.1 years. A total of 246 patients (78.3%) could complete 3 consecutive injections at 1-month intervals after the start of treatment; 57 patients (18.2%) did not attend monthly follow-up during the 1-year follow-up period following the 3 consecutive monthly injections. Overall, 39.8% of the patients were not able to fully comply with the ranibizumab treatment by PRN regimen for 1 year. Better visual acuity at baseline, smaller lesion size, living closer to the hospital, higher education and sociocultural level, and better financial status were determined as factors affecting patient compliance. The most frequent reasons to discontinue treatment were fear of injection, disbelief in the benefit of the treatment, financial limitations, continuation of treatment at another center, and comorbid systemic diseases.Patient compliance and success rates of anti-VEGF therapy may be increased by determining the factors affecting patient compliance and raising awareness about n-AMD among patients and their relatives. Therefore, research regarding the management of this type of AMD has been extensive and is ongoing.6Age-related macular degeneration (AMD) is a progressive and degenerative disorder of the retinal pigment epithelium, Bruch’s membrane, and choriocapillaris. It is the most common cause of central vision loss in people 65 years and older.3 The introduction of vascular endothelial growth factor (VEGF) inhibitor therapy into clinical practice has dramatically altered the prognosis of wet AMD. Randomized clinical trials on AMD demonstrate a significant improvement in patients treated with ranibizumab compared to the placebo group, and ranibizumab therapy is recommended monthly to achieve the most effective visual outcomes.6 However, as an alternative to monthly injections, many retina clinics prefer a regimen of 3 monthly intravitreal injections as a loading dose, followed by injections administered as necessary based on visual acuity, optical coherence tomography (OCT), and fundus fluorescein angiography (FFA) findings, because this approach is more feasible in clinical practice.13 Having to go to the hospital every month for injection or follow-up, depending on their clinical condition, negatively influences patient compliance for various reasons, therefore affecting the success and outcome of treatment.The main underlying factor in the pathogenesis of wet AMD is the formation of new vessels in the choroid layer.The aim of this study was to determine patients’ treatment compliance rates and the factors that affect compliance with treatment and follow-up in patients diagnosed with wet AMD and recommended for ranibizumab therapy.The medical records of patients examined and diagnosed with wet AMD between February 2009 and February 2012 were analyzed retrospectively. A total of 314 patients who were recommended intravitreal ranibizumab injection (IVRI) therapy and who provided consent after being informed of the treatment regimen and duration were included in the study. The study was conducted in accordance with the Declaration of Helsinki and was approved by the Afyon Kocatepe University, Ethics Committee for Clinical Trials (2013/4 Decision: 42). Informed consent forms were obtained from all patients.The patients were diagnosed with AMD based on clinical, OCT, and FFA findings. Best corrected visual acuity (BCVA) was assessed using the Early Treatment Diabetic Retinopathy Study chart. All patients were informed that the first 3 injections were requisite, after which they would be examined monthly and injections would be repeated as necessary. At the follow-up appointments, all patients underwent ophthalmologic examination and OCT imaging, while FFA was performed only when needed. The treatment regimen consisted of 3 consecutive monthly injections followed by additional injections given when deemed necessary according to OCT and visual acuity findings.Patients’ demographic features and ocular characteristics were recorded from their records. We determined the number of patients who continued treatment and follow-up appointments for 1 year from the time of diagnosis and investigated the reasons for unsuccessful treatment and follow-up. All patients included in the study were contacted by phone and they or their relatives were asked predetermined questions in order to identify factors that may affect treatment compliance . PatientPatients were studied in 2 groups according to their compliance to IVRI treatment and the follow-up appointments for 1 year. Patients who regularly received 3 consecutive IVRI treatments after being diagnosed with wet AMD and were followed regularly for 1 year thereafter comprised the ‘compliant group’ (Group 1), while patients who did not regularly receive 3 consecutive IVRI treatments or could not be followed regularly for 1 year comprised the ‘noncompliant group’ (Group 2). Group 2 was further divided into 2 subgroups: patients who completed 3 consecutive months of IVRI treatment but who were unable to complete 1 year of follow-up and treatment (Group 2a), and patients who were unsuccessful in completing their 1 year of follow-up and treatment, including the initial 3 consecutive monthly IVRI injections (Group 2b).The data obtained were recorded and analyzed using a statistics software package . Because the data pertaining to factors affecting patient compliance were qualitative and grouped, chi-square test and chi-square automatic interaction detector (CHAID) analysis were used. P values below 0.05 were considered significant. The correlation between compliance and factors that may affect compliance was assessed using Cramer’s V analysis.The mean age of the 314 patients included in the study was 71.6±9.1 years; the study group comprised 160 female patients and 154 male patients. The number of patients who successfully completed 3 consecutive doses of IVRI treatment and were followed regularly for 1 year (Group 1) was 189 60.2%), while 125 (39.8%) patients showed inadequate compliance to treatment and follow-up (Group 2). Subgroup analysis of Group 2 showed that 57 patients (18.2%) completed 3 consecutive months of IVRI treatment following diagnosis but did not complete 1 year of follow-up (Group 2a), while 68 patients (21.6%) were not able to comply with follow-up and treatments including the initial 3 consecutive months of IVRI treatment (Group 2b). According to this, 246 patients (78.3%) completed 3 consecutive months of regular IVRI treatment. However, 57 (18.2%) of these patients were not able to regularly attend follow-up after the 3 consecutive IVRI treatments. The number of patients who were able to fully comply with their treatment and follow-up was 189 (60.2%)  and 2.%, while In the correlation analysis of data obtained from responses provided by patients and/or their relatives during the phone interview, statistically significant relationships emerged between patient compliance with the 1 year follow-up and IVRI treatment and an increase or decrease in the visual acuity of patients after treatment, the visual acuity in the affected eye at the time of diagnosis, how far from the hospital they lived, education level, sociocultural status, age, economic status, fear of injection, the size of the choroid neovascularization lesion detected with FFA, and retirement status (p<0.05). No statistically significant correlations were found between compliance with the 1 year follow-up and IVRI treatment and whether the patients were newly diagnosed or diagnosed in the past, whether they were previously diagnosed with or treated for age-related macular degeneration, the visual acuity level in the fellow eye at the time of diagnosis, the side and number of eyes involved, or patients’ age and employment status .From the results of CHAID analysis, it was determined that the patients’ treatment response in terms of visual acuity was the factor that may have the greatest effect on patient compliance with the 1 year follow-up and treatment. Compliance rates were high among patients whose visual acuity values increased or decreased following treatment, while visual acuity alone showed no positive effect on compliance when it remained unchanged . In the The patients provided between 1 and 4 reasons for not complying with the recommended IVRI treatment and 1 year follow-up. Among the 232 reasons stated by the 125 patients who failed to comply with follow-up and treatment, the most common was a fear of intravitreal injection (29.6%). This was followed by disbelief that treatment would be beneficial/resignation to one’s fate (21.6%), financial difficulty (20.8%), residing in another province or continuing with treatment in another province (20%), comorbid systemic diseases (18.4%), dissatisfaction with the outpatient clinic or operating room conditions (17.6%), lack of relatives to help the patient come to the hospital or not having enough time (16%), and difficulty in coming and going due to old age (16%) .When we examined the less common reasons, we found that 7 patients (5.6%) stopped attending follow-up because of improved vision and reduced visual complaints after IVRI treatment, but 5 of those patients presented to our clinic again after an average of 6 months due to deteriorating vision and increased visual complaints. Six patients (4.8%) were lost to follow-up due to mortality. The cause of death was cerebrovascular events in 3 patients, heart attack in 2 patients, and traffic accident for 1 patient. Of the patients who were unable to appear regularly to follow-up appointments, 6 (4.8%) were unable to find time due to their job, 5 (4%) were unable to find time due to caring for their spouse who was ill or bedbound, 4 (3.2%) had had a traffic accident a short time before the appointment date, and 3 (2.4%) were unable to come due to severe winter weather conditions.In this study, we observed that a significant portion of wet AMD patients did not comply adequately with the AMD treatment and follow-up protocol. The factors which had the greatest influence on whether patients continued their treatment were visual acuity change with treatment, visual acuity at the time of diagnosis, and distance to the treatment center.6 Unlike the monthly injections given in clinical trials, however, a regimen of monthly follow-up examinations and additional injections applied as necessary after the first 3 injections is more common in clinical practice worldwide. Some regimens use change in visual acuity during follow-up as the criterion for needing additional injections, while other clinics use the stabilization criterion. According to the stabilization approach, treatment is suspended if vision and anatomy have not shown further improvement in the last 3 follow-up visits, and is reinitiated and continued according to the stabilization criterion in the event of recurrence.13 Because clinical practice requires patients to continue attending monthly follow-up, treatment compliance rates may vary depending on factors that push the limits of patients’ compliance with treatment and patients’ level of awareness in terms of the disease and its treatment. While anti-VEGF therapy is promising for AMD patients, the need for repeated intraocular injections makes it difficult to successfully implement. This affects the efficacy and outcomes of treatment.Controlling angiogenesis with anti-VEGF therapy, which is now the standard treatment modality for wet AMD patients, prevents further macular damage by inhibiting the growth of new vessels and thus stabilizes vision. However, since the underlying pathology continues, anti-VEGF injections need to be continued repeatedly to control angiogenesis. Clinical trials have reported the long-term outcomes of patients complying with the study protocol, and successful treatment outcomes have been achieved.14 investigated the factors and problems affecting compliance with anti-VEGF treatment in AMD in real-life conditions and found a compliance rate of 81.1%. Reasons reported for inability to continue follow-up and treatment included not benefiting from treatment, severe comorbid systemic conditions, continuing treatment at another center, refusing treatment, and death. In addition, similar to our study, distance to the hospital and the necessity for a companion were found to be among the factors that made compliance difficult for patients. In another study with a similar purpose, compliance rates were reported as over 90% in the stabilization phase of treatment and 63.2% in the maintenance phase. Patient compliance was found to depend on the duration of treatment, visual acuity in the fellow eye, and functional outcomes of the initial treatment administered to the affected eye.15 In their study investigating the reasons for discontinuing IVRI, Vaze et al.16 found that 42.3% of the patients did not continue treatment for various reasons including their doctor ending treatment, frequent visits, difficulty of attendance and follow-up, financial limitations, pain, disbelief in the benefit of the treatment, and refusal of continuance of treatment due to comorbid systemic conditions. Other reasons given were continuing treatment at another center and being unable to continue treatment due to death.It has not been adequately addressed in the literature whether or not patients adequately comply with the intravitreal anti-VEGF treatment protocol in wet AMD due to the frequent and repeated injections. As far as we can determine, this subject has not yet been studied in our country, and the few studies conducted abroad have focused more on the reasons why patients discontinue treatment. Droege et al.18 These studies determined rates of discontinuing treatment or follow-up to be 4.2%, 8.1%, and 14.2%. When other studies are also considered, the rates of noncompliance with or discontinuation of treatment range between 4.2% and 42.3% in the literature. The differences in compliance rates between studies may be due to differences in the social and financial means and sociocultural levels of the patient populations and/or differences in methodology and follow-up duration between studies.In addition to factors that may affect patients’ compliance with intravitreal injection therapy and follow-up, some studies on the efficacy of intravitreal injection therapy have investigated reasons why some patients terminate treatment as a subtopic.Unlike in other studies, in the present study we attempted to investigate all factors that may have a positive or negative effect on compliance with IVRI treatment by examining not only the characteristics of patients who either discontinued treatment or did not comply adequately, but also the characteristics of patients who were adequately compliant with treatment and follow-ups, in order to identify solutions for increasing patient compliance.While patients’ financial means, education level, sociocultural values, disease awareness, and access to treatment are better in developed countries compared to developing or undeveloped countries, the tendency to live alone in old age is more common in developed countries due to the nature of society. This may cause the factors influencing patient compliance to differ from country to country. Health workers, especially ophthalmologists, patients themselves and their relatives, and the authorities that govern health policies all share the great responsibility of improving factors that may affect patient compliance. For example, fear of injection and not benefiting as expected from treatment were found to be the most common reasons stated by patients in our study for not complying adequately with the treatment and 1 year follow-up. This highlights the responsibility of ophthalmologists to properly inform patients about the pathogenesis, course, and treatment of AMD and what treatment responses they should expect.In Turkey, patients with health insurance have to pay a certain portion of the price of ranibizumab. In addition to this, high transportation costs can be a serious problem for patients and their families whose financial means are limited. Due to the large numbers of patients, the amount of time allotted to patients in outpatient clinics and operating rooms is minimized. Major steps must be taken in the development of policies to ensure that these conditions positively affect patients’ compliance with follow-up and treatment.Due to its nature, AMD usually emerges in very old patients. Many patients with AMD have a comorbid systemic disease. In our study, 74.3% of the patients had comorbid conditions. In terms of compliance, systemic disease was present in 73.7% of the noncompliant patients and 74.6% of the compliant patients. Although this is not a statistically significant difference, it shows that comorbid systemic disease is the reason that a substantial proportion of patients in this age group were unable to comply adequately. Here again, important responsibility falls on ophthalmologists in terms of explaining every aspect of AMD to patients, and on family physicians in terms of informing patients that postponing their eye examinations may lead to a serious threat to their visual acuity or cause them to miss the effective window for treating AMD.It is noteworthy that an increase or decrease in final BCVA in the affected eye following treatment emerged in statistical analysis as the most important factor affecting patient compliance. The positive aspect of this result may show that visual success is better in patients with a high level of compliance to treatment, which is expected. However, a decrease in the final BCVA has a positive effect on a patient’s compliance with follow-up and treatment because it evokes the fear of possibly losing one’s vision. Compliance is a necessary but not sufficient condition for successful visual outcomes. Hence, we found a group of patients in our study who did not comply adequately despite their visual acuity having improved with treatment. There may also be factors that make visual success difficult despite adequate compliance, such as disease severity and resistance. In these cases, it is clear that raising the patient’s level of awareness should increase patient compliance. BCVA in the affected eye at time of diagnosis emerged as another important factor and was inversely proportional to compliance, indicating that patients with lower vision at the time of diagnosis were more compliant with treatment and monthly follow-up. This may also have been a result of fear of vision loss. Studies including larger case series that investigate all factors and reasons for noncompliance, in addition to those analyzed in this study, may help to increase patients’ rate of compliance with intravitreal injection therapy.The limitations of our study are its retrospective design and the subjective nature of the answers to the questions asked by phone. It is possible that the answers were incomplete or biased.In conclusion, although acceptance of and compliance with treatment seem to be relatively high initially in patients with wet AMD recommended for IVRI therapy, a significant proportion of these patients are unable to fully comply with the treatment regimen within the 1-year follow-up period due to the stated reasons. However, in the time period our study analyzes, intravitreal injection therapy was newly becoming common among AMD patients. The behavioral characteristics of patients with regard to compliance with treatment may have changed in subsequent years. A new study is currently being conducted in our clinic investigating how patient behavior has changed in later years. Determining the factors that may affect treatment compliance in wet AMD patients and raising the awareness of patients and their relatives may facilitate the improvement of treatment compliance and success rates.


A digital impression of the mandibular molars of these participants was made by two operators with different levels of clinical experience, 3 or 16 years, using an intra-oral scanner . A silicone impression also was made by the same operators using the double mix impression technique . Stereolithography (STL) data were directly exported from the Lava COS system, while STL data of a plaster model made from silicone impression were captured by a three-dimensional (3D) laboratory scanner . The STL datasets recorded by two different operators were compared using 3D evaluation software and superimposed using the best-fit-algorithm method  for each impression technique. Inter-operator reproducibility as evaluated by average discrepancies of corresponding 3D data was compared between the two techniques (Wilcoxon signed-rank test).The visual inspection of superimposed datasets revealed that discrepancies between repeated digital impression were smaller than observed with silicone impression. Confirmation was forthcoming from statistical analysis revealing significantly smaller average inter-operator reproducibility using a digital impression technique (0.014± 0.02 mm) than when using a conventional impression technique (0.023 ± 0.01 mm).in vivo study suggest that inter-operator reproducibility with a digital impression technique may be better than that of a conventional impression technique and is independent of the clinical experience of the operator.The results of this  To date, no in vivo study investigating the accuracy of this impression technique has been reported. Accuracy can only be evaluated in comparison, preferably with a gold standard; which is not easy to establish in the oral cavity. Regarding precision, there is only a limited number of in vivo studies in the literature [A significant change taking place this century is the introduction of digital technology into dental practice; “Digital Dentistry” is becoming more prevalent each year. Recently, digital impression techniques with three-dimensional (3D) intra-oral scanners have been attracting attention gaining in popularity around the world . These iin vitro ,13–17,18terature ,20 and nin vivo. The null hypothesis of this study was that “there is no difference between the inter-operator reproducibilities of the 3D morphological data captured by the digital impression and conventional impression techniques”.Therefore, this study focused on the inter-operator reproducibility of 3D morphological data captured by a digital impression technique and compared the data to those captured as a result of a convention impression technique Twelve participants with a complete natural dentition were included in this study . Impressions of the mandibular right second premolar and the first and second molars of these participants were made by two operators with differing levels of clinical experience; one had 3 years of clinical experience (novice dentist) and the other had 16 years clinical experience (experienced dentist). For each participant, each operator employed 2 different techniques, an intra-oral scanner or silicone impression material. All impressions procedures were made in a controlled environment with a room temperature of 24.5±0.9°C and humidity of 30.2±1.7%. In total, forty-eight impressions were made (n = 12). All experimental procedures were approved by the Ethics Committee of Showa University . The participants provided written informed consent to participate in this study.An intra-oral scanner  was used to make digital impressions. In accordance with manufacturer’s instructions, a dusting powder  was used to pre-treat the surface of the teeth and then digital optical scanning was performed in one continuous scan without any pausing and resuming, starting from the occlusal surface and then moving to the lingual and buccal surfaces. Stereolithography (STL) data obtained by digital scanning were directly exported from the Lava COS system and stored in the laboratory computer .Whole arch conventional impressions were made with a vinylpolysiloxane silicone impression material (addition silicone)  using a double mix impression technique and standard metal stock trays , which had been carefully chosen to ensure adequate space for impression material. Tray adhesive was not applied to the selected tray, and the heavy body type impression material was injected into the tray using an automatic kneading device. The light type impression material was poured into the corresponding tooth using a syringe, and then the tray was inserted in the oral cavity and pressed to the tooth arch. After a 2-minute setting time, impressions were removed from the oral cavity, disinfected for 10 minutes and stored for 3 hour at room temperature and ambient humidity. Plaster models, fabricated with dental stone  according to manufacturer’s instructions, were then scanned with a dental CAD/CAM 3D laser scanner  using the highly accurate protocol for scanning large objects. Scan data of the premolar and molar regions were exported in the STL data format and stored in the laboratory computer .First, 3D images constructed from STL data were displayed and trimmed to the tooth shape and gingival margin using appropriate software . These trimmed STL data obtained from novice and experienced dentists were loaded onto a 3D evaluation software platform and superimposed using the best-fit-algorithm method (least-squares method) to match 2 surfaces ,20. The The average discrepancies of all measurement points in absolute values were calculated for 2 techniques for each participant. In addition, the average discrepancy for all 12 participants, which represented the inter-operator reproducibility of each technique, was calculated.In order to evaluate the precision of the laboratory scanner, which may influence on the precision of scanned data, laboratory scanning of a cast model was repeated 5 times and the acquired 10 data set pairs were compared using the best-fit-algorithm as described above. These procedures were repeated for the oral scanner in order to test the precision in the laboratory settings.in vitro reproducibility of the laboratory scanner was compared with that of the oral scanner by independent t-test. All statistical analyses were performed using SPSS version 22 , and the level of significance was set at 0.05.The average discrepancies of all measurement points in absolute values were calculated and compared between the 2 techniques for each participant by independent t-test. In addition, the average discrepancies for all 12 participants were also compared between the 2 techniques by Wilcoxon signed-rank test. The average The average discrepancy data for every participant calculated by using the best-fit-algorithm method are summarized in The average precision of 10 pairs of measurements with the laboratory scanner and the intraoral scanner was 0.007 ± 0.0007 and 0.006 ± 0.0017 mm, respectively, and no significant difference was observed.These results of this study lead us to reject the null hypothesis of this study that “there is no difference between the inter-operator reproducibilities of the 3D morphological data captured by the tested digital impression and conventional impression techniques”. More specifically, the study results suggest that inter-operator reproducibility of the digital impression technique is higher than that of the conventional impression technique.The merits of digital direct scanning techniques over conventional impression techniques have been well documented as described in the introduction section. Although digital impression is reported to be associated with inevitable inaccuracy sources, such as presence of saliva, movement of the patient’s jaw, or stitching of multiple digital images. One of the most clinically important benefits is that a digital impression is not vulnerable to unavoidable inaccuracies associated with the dimensional changes of impression materials and dental stones that may lead to misfit of dental prostheses.in vitro [in vivo clinical evaluations of are vital in order to demonstrate translation of in vitro finding to clinical significance in vivo. However, accuracy, which represents trueness, is difficult to evaluate in vivo because the real dimensions of the test participant, the gold standard (ISO 5725–1) [in vivo evaluations of accuracy are often performed by measuring the fit of final restorations [Several laboratory-based studies report excellent dimensional accuracy and precision from digital impressions compared to conventional impressions in vitro , 13–17.  5725–1) ,28, cannorations ,29,30. Sorations ,31–34. Iin vivo [Precision of impression technique is best assessed by superimposing entire scanned images captured using a given method several times ,17,20,35in vivo ,36 and net al. (2016) who evaluated 2 conventional and 7 digital impression systems in 5 participants [in vivo and also reported significant variation in the level of precision depending upon the system tested. Our study results are in general agreement. A clear improvement of our study is the higher number of the participants we included and that we conducted a systematic analysis of the inter-operator reproducibility. The latter is particularly clinically important because silicone impressions are notoriously sensitive to the skill and experience level of the clinician who is making the impression [The current study is best compared to the results of Ender icipants . They repression ,12. Of iet al. 16 who evpression –41.Another source of error might be the difference in clinician skill level. Interestingly, the most significant discrepancies between repeated recordings were found on the lingual distal surface of the molar for the silicone impression technique. This finding illustrates well the clinical situation because this region is prone to contamination by saliva and difficult for novice dentists to manage and make an accurate impression. Furthermore, the distal region of second molars might not be fully covered or impression material may not be adequately supported by the impression tray, which propagates distortion of the impression material under the influence of the weight of the plaster during the pouring process. Again, these factors are influenced by the condition of the patient and the skill level of the operator and regarded as impactful reasons why the silicone impression technique exhibits poorer inter-operator reproducibility than digital impression techniques. It should be noted that our study did not examine accuracy but precision and employed only one operator in each clinical experiences, which does not allow drawing a conclusion that the clinical experience was the definitive influencing factor. However, an important finding from our study is that the improved reproducibility of digital impressions compared to silicone impressions, was consistent and independent of participant , suggestLastly, although the difference in the average discrepancy between the two techniques was as small as 0.009 mm, which was not considered clinically relevant, our result suggesting better precision with the digital impression method than with the gold standard method might be a good reason for clinicians to apply this method in clinical settings.in vivo.This study exclusively investigated three natural mandibular teeth in healthy participants. We did not investigate prepared abutment teeth, which could be a limitation since both shape and characteristics of a tooth surface may influence accuracy and/or precision of an impression technique. Another limitation might be that this study only tested precision of the technique, whereas clinical relevance might be evaluated by measuring the fit of fabricated prosthesis. We suggest future studies if preliminary studies like ours have demonstrated clinically acceptable inter-operator reproducibility in vivo study suggest that a digital impression technique yields superior reproducibility compared to conventional impression technique. This advantage is independent of an operator’s clinical experience of the operator and of the oral condition of the patient.The result of this


Additionally, we used a curated text-mining analysis of the literature to identify novel putative LIR motif-containing proteins (LIRCPs) in viruses. We anticipate that iLIR@viral will assist with elucidating the full complement of LIRCPs in viruses.Macroautophagy/autophagy has been shown to mediate the selective lysosomal degradation of pathogenic bacteria and viruses (xenophagy), and to contribute to the activation of innate and adaptative immune responses. Autophagy can serve as an antiviral defense mechanism but also as a proviral process during infection. Atg8-family proteins play a central role in the autophagy process due to their ability to interact with components of the autophagy machinery as well as selective autophagy receptors and adaptor proteins. Such interactions are usually mediated through LC3-interacting region (LIR) motifs. So far, only one viral protein has been experimentally shown to have a functional LIR motif, leaving open a vast field for investigation. Here, we have developed the iLIR@viral database ( Autophagy is a multistep process that consists of the isolation of cytoplasmic components into double-membrane vesicles, called autophagosomes, that shuttle to lysosomes, which serve as end-point degradative organelles. It is a catabolic mechanism that enables the removal of damaged or excess cellular organelles and proteins, thereby contributing to the maintenance of cell homeostasis and survival.,,The autophagic machinery is highly conserved from unicellular eukaryotes to metazoans. Among the proteins that take part in this process, the Atg8-family proteins play a central role.,LC3-interacting region  critical for the binding to Atg8-family proteins.,,[WFY][DEILQTV][ADEFHIKLMPSTV][ILV], where the residues in positions 3 and 6 correspond to the most crucial ones for the interaction with Atg8-family proteins.Although originally considered to be a nonselective bulk degradation mechanism, a gathering body of evidence over the past decade suggests that autophagy is much more selective than initially appreciated. Selective targeting of cellular components to autophagosomes for degradation relies on the existence of selective autophagy receptors able to recognize and tether cargos toward nascent autophagosomes.,,,Besides its role in cellular homeostasis, autophagy is also involved in the innate immune response against pathogens.http://ilir.uk/virus/), that organizes information on the presence of LIR motifs in viral proteins. Additionally, a curated text-mining analysis of the literature permitted us to predict functional LIR motifs in viral proteins that have already been shown to associate with Atg8-family members.We have developed a database, iLIR@viral  to name the species, genus and families of each of the viruses cited in the database, and the Baltimore classification system that groups viruses depending on their genome and kind of replication  (see Methods).,The iLIR@viral database is a web resource freely available to the academic community at The ‘Search’ menu allows the user to look in the database for a specific protein or virus order, family, subfamily, genus, species or common name. Uniprot identifiers can also be used in the search function.,The BLAST  menu offers the user to search the database using a protein sequence as query against the reviewed set of viral proteins from UniProt database. We have used Position-Specific Iterative (PSI) BLAST to search against the database.https://ilir.warwick.ac.uk) to identify LIRCPs in viruses (see Methods for details).,We have used the iLIR web resource  from HIV-1 binds to all Atg8-family proteins, and matrix protein 2 (M2) from influenza was shown to bind to LC3. Yet, influenza M2 protein is the only one that contains a LIR motif that has been experimentally validated.,The protein M2 from influenza A virus is necessary and sufficient for the inhibition of the autophagic degradation of the virus by blocking the fusion between the autophagosomes and lysosomes.,We were also able to identify one xLIR motif (11-EGWQTI-16) in the sequence of the accessory viral protein Nef of the virus HIV-1 group M subtype B (strain 89.6). Nef colocalizes with LC3 and BECN1, and contributes to the inhibition of autophagic maturation, thus protecting the virus from elimination by autophagy.,The proteins TRS1 from human cytomegalovirus and neurovirulence factor ICP34.5 from human herpesvirus (HSV) both interact with BECN1 via a specific BECN1-binding domain. This interaction is required for the inhibition of autophagosome maturation and fusion with the lysosomes.We observed that 7% of the reviewed sequences that contains at least one putative LIR motif correspond to the genome polyprotein from various viruses. Because polyproteins are processed co- and post-translationally by both host and viral proteases, we ran a systematic PubMed search with the terms ‘name of the virus + autophagy’ followed by ‘name of the virus + LC3’ to restrain the result outcome as necessary, finally we looked for papers (excluding reviews and commentaries) that specifically mention proteins derived from the processing of the viral genome polyprotein.,Our literature searching strategy pinpointed several nonstructural viral proteins; one of those was the protein NS1 from Dengue viruses. Studies have shown that NS1 protein from Dengue virus type 2 (DENV-2) colocalizes with LC3 and that DENV-2 particles and autophagosomes travel together during viral infection.,,,Other nonstructural proteins from different viruses interact with LC3 proteins. For instance, the nonstructural protein NS5A from Hepatitis C virus that colocalizes and can be coimmunoprecipitated with LC3 proteins when ectopically expressed in various hepatoma cell lines.,Finally, we were able to identify proteins from Zika virus that have been just recently related to autophagy. Independent studies have shown that Zika virus activates autophagy and that the formation of autophagosomes is crucial to the replication of the virus.Autophagy is an evolutionarily conserved and highly regulated, intracellular catabolic mechanism that is essential for maintaining homeostasis and coping with nutrient starvation. It is increasingly appreciated that autophagy can be highly selective, and that xenophagy, the selective autophagy of pathogens, is an important aspect of the immune response, which protects against infection. A vast array of viruses are associated with autophagy, and we have found several viral proteins containing putative LIR motifs that are thought to interact with the autophagic machinery via Atg8-family proteins. A continued research effort to better understand how these viral proteins interact with the autophagic machinery may provide therapeutic strategies and ultimately lead to the discovery of novel pharmacological agents to fight viral infections.http://www.uniprot.org/ [Accessed 20 September 2016]. xLIR and WxxL patterns for these proteins were identified using the approach suggested previously.,Protein sequences of all reviewed viral proteins were downloaded from Uniprot database vailable at: https://talk.ictvonline.org/files/master-species-lists/m/msl/5945 [Accessed 20 September 2016].The taxonomic lineage obtained from UniProt for all the reviewed viral proteins correspond to the Baltimore classification system. To do the conversion between the Baltimore and ICTV classification systems, we matched the organism name for each reviewed sequence from UniProt with the organism names obtained from the ICTV master species list 2015 v1, available at: The differences between the classification systems were identified through a battery of SQL queries. The details of these are attached in Tables S5, S6 and S7. Levenshtein distance  was used to compare the species name that belongs to a particular genus and family between both the classification systems. Levenshtein distance is defined as the minimal number of characters required to replace, insert or delete to transform one string into another. The Levenshtein distance is symmetric and it holds:http://search.cpan.org/CPAN/authors/id/J/JH/JHI/String-Approx-3.27.tar.gz) The closer the value of Levenshstein distance to zero, the closer are the species names.Here, ‘x’ and ‘y’ are 2 strings and d is the distance between ‘x’ and ‘y’ put as minimal cost of operations to transform ‘x’ to ‘y’. The complexity of the algorithm is O(m*n), where n and m are the lengths of 2 strings.Using this approach, we could reliably justify the ICTV classification of 14055 out 15589 proteins loaded into the database.http://ilir.uk/virus. Through the website, users can navigate for LIRCPs using both Baltimore and ICTV Virus classification systems.To share the information beyond our MySQL (v5.6.33) DBMS (Database Management System), we built a website using HTML, CSS, JavaScript and PHP (v5.6.27) technologies. It is hosted at