Infection of ectocervical tissue and universal targeting of T-cells mediated by primary non-macrophage-tropic and highly macrophage-tropic XXXX R5 envelopes.

@entity1 @entity18341 @entity404 @entity2858 @entity281 @entity791
BACKGROUND: @entity2858 variants carrying non-macrophage-tropic @entity2858 R5 envelopes (Envs) are predominantly transmitted and persist in immune tissue even in @entity791 @entity1 who have highly macrophage-tropic variants in the brain. Non-macrophage-tropic R5 Envs require high levels of @entity404 for @entity281 contrasting with macrophage-tropic Envs, which can efficiently mediate @entity281 of cells via low @entity404 . Here, we investigated whether non-macrophage-tropic R5 Envs from the acute stage of @entity281 (including transmitted/founder @entity18341 ) mediated more efficient @entity281 of ectocervical explant cultures compared to non-macrophage-tropic and highly macrophage-tropic R5 Envs from late disease. RESULTS: We used @entity18341 + pseudovirions that carried a GFP reporter gene to measure @entity281 of the first cells targeted in ectocervical explant cultures. In straight titrations of @entity18341 + pseudovirus supernatants, mac-tropic R5 Envs from late disease mediated slightly higher infectivities for ectocervical explants although this was not significant. Surprisingly, explant @entity281 by several T/F/acute Envs was lower than for Envs from late disease. However, when infectivity for explants was corrected to account for differences in the overall infectivity of each @entity18341 + pseudovirus (measured on highly permissive HeLa TZM-bl cells), non-mac-tropic early and late disease @entity18341 + pseudoviruses mediated significantly higher @entity281 . This observation suggests that cervical tissue preferentially supports non-mac-tropic @entity18341 + viruses compared to mac-tropic viruses. Finally, we show that T-cells were the main targets for @entity281 regardless of whether explants were stimulated with T-cell or monocyte/macrophage cytokines. There was no evidence of macrophage @entity281 even for pseudovirions carrying highly mac-tropic Envs from brain tissue or for the highly mac-tropic, laboratory strain, BaL, which targeted T-cells in the explant tissue. CONCLUSIONS: Our data support ectocervical tissue as a favorable environment for non-mac-tropic @entity2858 R5 variants and emphasize the role of T-cells as initial targets for @entity281 even for highly mac-tropic variants.
