T cell-tropic HIV efficiently infects alveolar macrophages through contact with infected CD4+ T cells
Abstract Alveolar macrophages (AMs) are critical for defense against airborne pathogens and AM dysfunction is thought to contribute to the increased burden of pulmonary infections observed in individuals living with HIV-1 (HIV). While HIV nucleic acids have been detected in AMs early in infection, c...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/0c180a3a227b47598d0db0a78f5b3e8a |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:0c180a3a227b47598d0db0a78f5b3e8a |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:0c180a3a227b47598d0db0a78f5b3e8a2021-12-02T14:03:46ZT cell-tropic HIV efficiently infects alveolar macrophages through contact with infected CD4+ T cells10.1038/s41598-021-82066-x2045-2322https://doaj.org/article/0c180a3a227b47598d0db0a78f5b3e8a2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82066-xhttps://doaj.org/toc/2045-2322Abstract Alveolar macrophages (AMs) are critical for defense against airborne pathogens and AM dysfunction is thought to contribute to the increased burden of pulmonary infections observed in individuals living with HIV-1 (HIV). While HIV nucleic acids have been detected in AMs early in infection, circulating HIV during acute and chronic infection is usually CCR5 T cell-tropic (T-tropic) and enters macrophages inefficiently in vitro. The mechanism by which T-tropic viruses infect AMs remains unknown. We collected AMs by bronchoscopy performed in HIV-infected, antiretroviral therapy (ART)-naive and uninfected subjects. We found that viral constructs made with primary HIV envelope sequences isolated from both AMs and plasma were T-tropic and inefficiently infected macrophages. However, these isolates productively infected macrophages when co-cultured with HIV-infected CD4+ T cells. In addition, we provide evidence that T-tropic HIV is transmitted from infected CD4+ T cells to the AM cytosol. We conclude that AM-derived HIV isolates are T-tropic and can enter macrophages through contact with an infected CD4+ T cell, which results in productive infection of AMs. CD4+ T cell-dependent entry of HIV into AMs helps explain the presence of HIV in AMs despite inefficient cell-free infection, and may contribute to AM dysfunction in people living with HIV.Abigail E. SchiffAlice H. LinderShillah N. LuhemboStephanie BanningMartin J. DeymierThomas J. DiefenbachAmy K. DickeyAthe M. TsibrisAlejandro B. BalazsJosalyn L. ChoBenjamin D. MedoffGerhard WalzlRobert J. WilkinsonWendy A. BurgersBjörn CorleisDouglas S. KwonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Abigail E. Schiff Alice H. Linder Shillah N. Luhembo Stephanie Banning Martin J. Deymier Thomas J. Diefenbach Amy K. Dickey Athe M. Tsibris Alejandro B. Balazs Josalyn L. Cho Benjamin D. Medoff Gerhard Walzl Robert J. Wilkinson Wendy A. Burgers Björn Corleis Douglas S. Kwon T cell-tropic HIV efficiently infects alveolar macrophages through contact with infected CD4+ T cells |
| description |
Abstract Alveolar macrophages (AMs) are critical for defense against airborne pathogens and AM dysfunction is thought to contribute to the increased burden of pulmonary infections observed in individuals living with HIV-1 (HIV). While HIV nucleic acids have been detected in AMs early in infection, circulating HIV during acute and chronic infection is usually CCR5 T cell-tropic (T-tropic) and enters macrophages inefficiently in vitro. The mechanism by which T-tropic viruses infect AMs remains unknown. We collected AMs by bronchoscopy performed in HIV-infected, antiretroviral therapy (ART)-naive and uninfected subjects. We found that viral constructs made with primary HIV envelope sequences isolated from both AMs and plasma were T-tropic and inefficiently infected macrophages. However, these isolates productively infected macrophages when co-cultured with HIV-infected CD4+ T cells. In addition, we provide evidence that T-tropic HIV is transmitted from infected CD4+ T cells to the AM cytosol. We conclude that AM-derived HIV isolates are T-tropic and can enter macrophages through contact with an infected CD4+ T cell, which results in productive infection of AMs. CD4+ T cell-dependent entry of HIV into AMs helps explain the presence of HIV in AMs despite inefficient cell-free infection, and may contribute to AM dysfunction in people living with HIV. |
| format |
article |
| author |
Abigail E. Schiff Alice H. Linder Shillah N. Luhembo Stephanie Banning Martin J. Deymier Thomas J. Diefenbach Amy K. Dickey Athe M. Tsibris Alejandro B. Balazs Josalyn L. Cho Benjamin D. Medoff Gerhard Walzl Robert J. Wilkinson Wendy A. Burgers Björn Corleis Douglas S. Kwon |
| author_facet |
Abigail E. Schiff Alice H. Linder Shillah N. Luhembo Stephanie Banning Martin J. Deymier Thomas J. Diefenbach Amy K. Dickey Athe M. Tsibris Alejandro B. Balazs Josalyn L. Cho Benjamin D. Medoff Gerhard Walzl Robert J. Wilkinson Wendy A. Burgers Björn Corleis Douglas S. Kwon |
| author_sort |
Abigail E. Schiff |
| title |
T cell-tropic HIV efficiently infects alveolar macrophages through contact with infected CD4+ T cells |
| title_short |
T cell-tropic HIV efficiently infects alveolar macrophages through contact with infected CD4+ T cells |
| title_full |
T cell-tropic HIV efficiently infects alveolar macrophages through contact with infected CD4+ T cells |
| title_fullStr |
T cell-tropic HIV efficiently infects alveolar macrophages through contact with infected CD4+ T cells |
| title_full_unstemmed |
T cell-tropic HIV efficiently infects alveolar macrophages through contact with infected CD4+ T cells |
| title_sort |
t cell-tropic hiv efficiently infects alveolar macrophages through contact with infected cd4+ t cells |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/0c180a3a227b47598d0db0a78f5b3e8a |
| work_keys_str_mv |
AT abigaileschiff tcelltropichivefficientlyinfectsalveolarmacrophagesthroughcontactwithinfectedcd4tcells AT alicehlinder tcelltropichivefficientlyinfectsalveolarmacrophagesthroughcontactwithinfectedcd4tcells AT shillahnluhembo tcelltropichivefficientlyinfectsalveolarmacrophagesthroughcontactwithinfectedcd4tcells AT stephaniebanning tcelltropichivefficientlyinfectsalveolarmacrophagesthroughcontactwithinfectedcd4tcells AT martinjdeymier tcelltropichivefficientlyinfectsalveolarmacrophagesthroughcontactwithinfectedcd4tcells AT thomasjdiefenbach tcelltropichivefficientlyinfectsalveolarmacrophagesthroughcontactwithinfectedcd4tcells AT amykdickey tcelltropichivefficientlyinfectsalveolarmacrophagesthroughcontactwithinfectedcd4tcells AT athemtsibris tcelltropichivefficientlyinfectsalveolarmacrophagesthroughcontactwithinfectedcd4tcells AT alejandrobbalazs tcelltropichivefficientlyinfectsalveolarmacrophagesthroughcontactwithinfectedcd4tcells AT josalynlcho tcelltropichivefficientlyinfectsalveolarmacrophagesthroughcontactwithinfectedcd4tcells AT benjamindmedoff tcelltropichivefficientlyinfectsalveolarmacrophagesthroughcontactwithinfectedcd4tcells AT gerhardwalzl tcelltropichivefficientlyinfectsalveolarmacrophagesthroughcontactwithinfectedcd4tcells AT robertjwilkinson tcelltropichivefficientlyinfectsalveolarmacrophagesthroughcontactwithinfectedcd4tcells AT wendyaburgers tcelltropichivefficientlyinfectsalveolarmacrophagesthroughcontactwithinfectedcd4tcells AT bjorncorleis tcelltropichivefficientlyinfectsalveolarmacrophagesthroughcontactwithinfectedcd4tcells AT douglasskwon tcelltropichivefficientlyinfectsalveolarmacrophagesthroughcontactwithinfectedcd4tcells |
| _version_ |
1718392064494796800 |