UMMS Affiliation
Program in Molecular Medicine; Department of Microbiology and Physiological Systems; Department of Obstetrics and Gynecology
Publication Date
2015-06-09
Document Type
Article
Disciplines
Allergy and Immunology | Immune System Diseases | Immunology and Infectious Disease | Infectious Disease | Obstetrics and Gynecology | Virology | Virus Diseases
Abstract
BACKGROUND: HIV-1 variants carrying non-macrophage-tropic HIV-1 R5 envelopes (Envs) are predominantly transmitted and persist in immune tissue even in AIDS patients who have highly macrophage-tropic variants in the brain. Non-macrophage-tropic R5 Envs require high levels of CD4 for infection contrasting with macrophage-tropic Envs, which can efficiently mediate infection of cells via low CD4. Here, we investigated whether non-macrophage-tropic R5 Envs from the acute stage of infection (including transmitted/founder Env) mediated more efficient infection of ectocervical explant cultures compared to non-macrophage-tropic and highly macrophage-tropic R5 Envs from late disease.
RESULTS: We used Env+ pseudovirions that carried a GFP reporter gene to measure infection of the first cells targeted in ectocervical explant cultures. In straight titrations of Env+ pseudovirus supernatants, mac-tropic R5 Envs from late disease mediated slightly higher infectivities for ectocervical explants although this was not significant. Surprisingly, explant infection 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 Env+ pseudovirus (measured on highly permissive HeLa TZM-bl cells), non-mac-tropic early and late disease Env+ pseudoviruses mediated significantly higher infection. This observation suggests that cervical tissue preferentially supports non-mac-tropic Env+ viruses compared to mac-tropic viruses. Finally, we show that T-cells were the main targets for infection regardless of whether explants were stimulated with T-cell or monocyte/macrophage cytokines. There was no evidence of macrophage infection 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 HIV-1 R5 variants and emphasize the role of T-cells as initial targets for infection even for highly mac-tropic variants.
Keywords
Ectocervical explants, HIV-1 envelopes, Tropism, T-cells, Macrophages
Rights and Permissions
© 2015 Peters et al. Open Access - This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
DOI of Published Version
10.1186/s12977-015-0176-2
Source
Retrovirology. 2015 Jun 9;12:48. doi: 10.1186/s12977-015-0176-2. Link to article on publisher's site
Journal/Book/Conference Title
Retrovirology
Related Resources
PubMed ID
26055104
Repository Citation
Peters PJ, Gonzalez-Perez MP, Musich TA, Moore Simas TA, Lin R, Morse AN, Shattock RJ, Derdeyn CA, Clapham PR. (2015). Infection of ectocervical tissue and universal targeting of T-cells mediated by primary non-macrophage-tropic and highly macrophage-tropic HIV-1 R5 envelopes. Open Access Publications by UMass Chan Authors. https://doi.org/10.1186/s12977-015-0176-2. Retrieved from https://escholarship.umassmed.edu/oapubs/2572
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Allergy and Immunology Commons, Immune System Diseases Commons, Immunology and Infectious Disease Commons, Infectious Disease Commons, Obstetrics and Gynecology Commons, Virology Commons, Virus Diseases Commons