Preferential infection and depletion of <i>Mycobacterium tuberculosis</i>–specific CD4 T cells after HIV-1 infection

Geldmacher, Christof; Ngwenyama, Njabulo; Schuetz, Alexandra; Petrovas, Constantinos; Reither, Klaus; Heeregrave, Edwin J.; Casazza, Joseph P.; Ambrozak, David R.; Louder, Mark K.; Ampofo, William; Pollakis, Georgios; Hill, Brenna J.; Sanga, Erica; Saathoff, Elmar; Maboko, Leonard; Roederer, Mario; Paxton, William A.; Höelscher, Michael; Koup, Richard A.

doi:10.1084/jem.20100090

Cited by 211 publications

(267 citation statements)

References 51 publications

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“…Therefore, occurrence of HIV acquisition in vaccinated individuals most likely involves early exposure and infection of vulnerable CD4 T cells by HIV. Our group and others have shown that human CD4 T cells specific to different antigens demonstrate differential susceptibilities to HIV (8,9). Because vector-specific CD4 T cells are elicited by recombinant viral vector vaccines, it should be highly informative for future HIV vaccine design to investigate whether vector antigen-specific CD4 T cells induced by a given viral vectored HIV vaccine are particularly resistant or susceptible to HIV infection.…”

Section: Aids | Antigen-specific Cd4 T Cells | Viral Vectorsmentioning

confidence: 98%

Preferential infection of human Ad5-specific CD4 T cells by HIV in Ad5 naturally exposed and recombinant Ad5-HIV vaccinated individuals

Eller

Zafar

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Efforts to develop an efficacious HIV vaccine have been unsuccessful to date. Efficacy trials have reported that recombinant Ad5 (rAd5)-HIV vaccines were not efficacious and unexpectedly associated with excess HIV infection in vaccine recipients. Understanding the underlying mechanisms is urgent and will further HIV vaccine design. By comparing human CD4 T cells specific to Ad5 and CMV, we report that natural exposure- or vaccine-induced Ad5-specific CD4 T cells are highly susceptible to HIV compared with CMV-specific CD4 T cells and selectively manifest a Th17-like proinflammatory phenotype. Our findings suggest a potential mechanism for rAd5-associated excess HIV infections in vaccine recipients and highlight that testing HIV susceptibility of vaccine-generated CD4 T cells may have utility before vaccine evaluation in human trials.

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Section: Aids | Antigen-specific Cd4 T Cells | Viral Vectorsmentioning

confidence: 98%

Preferential infection of human Ad5-specific CD4 T cells by HIV in Ad5 naturally exposed and recombinant Ad5-HIV vaccinated individuals

Eller

Zafar

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…HIV-1-induced immunodeficiency leads to increased risk of newly acquired TB and adverse clinical outcomes. 2 Furthermore, HIV replication, diversity, persistence in tissue compartments and reservoirs complicate clinical outcomes and pose a threat to therapeutic management and cure strategies. 3,4 HIV-1 diversity is a function of its error-prone reverse transcriptase, replication rate, recombination, and host selective pressures.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Dominant HIV Quasispecies Suggests Independent Viral Evolution Within Spinal Granulomas Coinfected with Mycobacterium tuberculosis and HIV-1 Subtype C

Danaviah

Oliveira

Gordon³

et al. 2016

AIDS Research and Human Retroviruses

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Extrapulmonary tuberculosis (TB) is a significant public health challenge in South Africa and worldwide, largely fuelled by the HIV epidemic. In spinal TB, Mycobacteria infect the spinal column without dissemination to the spinal cord. The immune microenvironment, target cell characteristics, and other evolutionary forces within granulomas during HIV/TB coinfection are poorly characterized. We investigated whether spinal TB granulomas represent a sequestered anatomical site where independent HIV evolution occurs, and assessed the role of macrophages as a target cell for both HIV and mycobacteria. RNA was extracted from plasma and granulomatous tissue from six antiretroviral-naive HIV-1/spinal TB-coinfected patients, RT-PCR amplified, and the C2-V5 env segment was cloned and sequenced. Analysis of genetic diversity, phylogeny and coalescence patterns was performed on clonal sequences. To investigate their role in HIV sequestration, macrophages and the HIV-1 p24 protein were immune localized and ultrastructural features were studied. Intercompartment diversity measurements and phylogenetic reconstruction revealed anatomically distinct monophyletic HIV-1 clusters in four of six patients. Genotypic CCR5-tropic variants were predominant (98.9%) with conservation of putative N-linked glycosylation sites in both compartments. CD68+ reactivity was associated with higher tissue viral load (r = 1.0; p < 0.01) but not greater intrapatient diversity (r = 0.60; p > 0.05). Ultrastructural imaging revealed the presence of bacterial and virus-like particles within membrane-bound intracellular compartments of macrophages. Spinal tuberculosis granulomas may form anatomically discreet sites of divergent viral evolution. Macrophages in these granulomas harbored both pathogens, suggesting that they may facilitate the process of viral sequestration within this compartment.

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“…Dans la phase d'infection chronique qui précède le traitement antirétroviral, le VIH cible et élimine préférentiellement les lymphocytes T CD4 + spécifiques de Mtb, par comparaison aux T CD4 + spécifiques d'autres pathogènes, comme le CMV [22]. Ce ciblage pourrait s'expliquer par l'état de différenciation des T CD4 + spécifiques de Mtb, qui produisent plus d'interleukine-2 (IL-2) et moins de -chimiokines, telles que MIP-1 (macrophage inflam- 4), par comparaison aux cellules spécifiques de CMV, l'IL-2 favorisant la réplication du VIH et les -chimiokines inhibant cette réplication par l'occupation du corécepteur CCR5 (C-C chemokine receptor 5) [23]. La déplétion rapide des cellules T CD4 + spécifiques de Mtb durant l'infection à VIH peut expliquer pourquoi le test tuberculinique est fréquemment négatif chez les patients co-infectés et, plus généralement, pourquoi la tuberculose est une infection opportuniste prédo-minante lors de la progression vers le Sida.…”

Section: Mécanismes Possibles De L'iris Reconstitution Rapide Des Répunclassified

L’iris

Chakrabarti

Lortholary

2015

Med Sci (Paris)

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Preferential infection and depletion of Mycobacterium tuberculosis–specific CD4 T cells after HIV-1 infection

Abstract: HIV-1 preferentially infects M. tuberculosis-specific CD4+ T cells due to their increased production of IL-2.

Cited by 211 publications

References 51 publications

Preferential infection of human Ad5-specific CD4 T cells by HIV in Ad5 naturally exposed and recombinant Ad5-HIV vaccinated individuals

Preferential infection of human Ad5-specific CD4 T cells by HIV in Ad5 naturally exposed and recombinant Ad5-HIV vaccinated individuals

Analysis of Dominant HIV Quasispecies Suggests Independent Viral Evolution Within Spinal Granulomas Coinfected with Mycobacterium tuberculosis and HIV-1 Subtype C

L’iris

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