No evidence of HIV replication in children on antiretroviral therapy

Zyl, Gert van; Katusiime, Mary Grace; Wiegand, Ann; McManus, W. R.; Bale, Michael J.; Halvas, Elias K.; Luke, Brian T.; Boltz, Valerie F.; Spindler, Jonathan; Laughton, Barbara; Engelbrecht, Susan; Coffin, John M.; Cotton, Mark F.; Shao, Wei; Mellors, John W.; Kearney, Mary F.

doi:10.1172/jci94582

Cited by 65 publications

(67 citation statements)

References 43 publications

(76 reference statements)

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“…74 While cellular proliferation may expand some viral lineages, there is little evidence of viral replication during ART based on analyses of viral sequences in the blood (Refs. 75,76). A possible exception to this is in lymph node follicles where poor penetration of ART drugs 78 and CD8+ T cells 79 may facilitate HIV-1 replication in CD4+ follicular helper T (T FH ) cells despite therapy.…”

Section: Exploring the Preferences Of T Cell-tropic Virusesmentioning

confidence: 99%

The evolution of HIV-1 entry phenotypes as a guide to changing target cells

Joseph

Swanstrom

2018

Journal of Leukocyte Biology

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Summary Sentence: The R5 T cell-tropic form of HIV-1 is the most abundant form and the evolutionary precursor to X4 T cell-tropic and macrophage-tropic variants. AbstractThrough a twist of fate the most common form of HIV-1, as defined by entry phenotype, was not appreciated until recently. The entry phenotype is closely linked to the target cell and thus to virus-host interactions and pathogenesis. The most abundant form of HIV-1 uses CCR5 as the coreceptor and requires a high density of CD4 for efficient entry, defining its target cell as the CD4+ memory T cell. This is the transmitted form of the virus, the form that is found in the blood, and the form that rebounds from the latent reservoir. When CD4+/CCR5+ T cells become limiting the virus evolves to use alternative target cells to support viral replication. In the CNS, the virus can evolve to use a cell that displays only a low density of CD4, while maintaining the use of CCR5 as the coreceptor. When this evolutionary variant evolves, it must be sustaining its replication in either macrophages or microglial cells, which display only a low density of CD4 relative to that on T cells. In the blood and lymphoid system, the major switch late in disease is from T cells expressing CD4 and CCR5 to T cells expressing CD4 and CXCR4, with a change in coreceptor specificity. Thus the virus responds in two different ways to different environments when its preferred target cell becomes limiting.

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Section: Exploring the Preferences Of T Cell-tropic Virusesmentioning

confidence: 99%

The evolution of HIV-1 entry phenotypes as a guide to changing target cells

Joseph

Swanstrom

2018

Journal of Leukocyte Biology

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“…[21][22][23][24] Other groups have proposed that ongoing viral replication contributes to the maintenance of the VR, [25][26][27] but this has been challenged by others. [28][29][30][31] While the VR is seeded rapidly after infection, 32 the contributing role of peripheral blood and lymph nodes (LNs) has been challenged by the observation that, in animal models, viral rebound after ART interruption (ATi) could occur in the presence as well as in the absence of viral DNA in either compartment. 32,33 Thus, viral rebound may originate from anatomical sites that are different from peripheral blood and LNs.…”

Section: Introductionmentioning

confidence: 99%

Despite early antiretroviral therapy effector memory and follicular helper CD4 T cells are major reservoirs in visceral lymphoid tissues of SIV-infected macaques

et al. 2020

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Whereas antiretroviral therapy (ART) suppresses viral replication, ART discontinuation results in viral rebound, indicating the presence of viral reservoirs (VRs) established within lymphoid tissues. Herein, by sorting CD4 T-cell subsets from the spleen, mesenteric and peripheral lymph nodes (LNs) of SIVmac251-infected rhesus macaques (RMs), we demonstrate that effector memory (TEM) and follicular helper (TFH) CD4 + T cells harbor the highest frequency of viral DNA and RNA, as well of early R-U5 transcripts in ART-naïve RMs. Furthermore, our results highlight that these two CD4 T cells subsets harbor viral DNA and early R-U5 transcripts in the spleen and mesenteric LNs (but not in peripheral LN) of RMs treated with ART at day 4 post infection suggesting that these two anatomical sites are important for viral persistence. Finally, after ART interruption, we demonstrate the rapid and, compared to peripheral LNs, earlier seeding of SIV in spleen and mesenteric LNs, thereby emphasizing the importance of these two anatomical sites for viral replication dynamics. Altogether our results advance understanding of early viral seeding in which visceral lymphoid tissues are crucial in maintaining TEM and TFH VRs.

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“…Other studies could not recapitulate that the phylogenies are temporally structured. 65,66 More relevant to our review are the more direct anatomical insights the study by Lorenzo-Redondo et al 11 provides. Using traditional measures of compartmentalization (F st ), they find that blood and lymph are dynamically separated.…”

Section: Phyloanatomymentioning

confidence: 95%

“…pointed out that the original study may have been measuring the evolution that was ongoing in the shrinking nonlatent reservoir during the first six months of treatment. Other studies could not recapitulate that the phylogenies are temporally structured …”

Section: Application Of Population Genetic and Phylodynamic Methods Tmentioning

confidence: 99%

Virus dynamics and phyloanatomy: Merging population dynamic and phylogenetic approaches

Bons

Regoes

2018

Immunological Reviews

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In evolutionary biology and epidemiology, phylodynamic methods are widely used to infer population biological characteristics, such as the rates of replication, death, migration, or, in the epidemiological context, pathogen spread. More recently, these methods have been used to elucidate the dynamics of viruses within their hosts. Especially the application of phylogeographic approaches has the potential to shed light on anatomical colonization pathways and the exchange of viruses between distinct anatomical compartments. We and others have termed this phyloanatomy. Here, we review the promise and challenges of phyloanatomy, and compare them to more classical virus dynamics and population genetic approaches. We argue that the extremely strong selection pressures that exist within the host may represent the main obstacle to reliable phyloanatomic analysis.

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No evidence of HIV replication in children on antiretroviral therapy

Cited by 65 publications

References 43 publications

The evolution of HIV-1 entry phenotypes as a guide to changing target cells

The evolution of HIV-1 entry phenotypes as a guide to changing target cells

Despite early antiretroviral therapy effector memory and follicular helper CD4 T cells are major reservoirs in visceral lymphoid tissues of SIV-infected macaques

Virus dynamics and phyloanatomy: Merging population dynamic and phylogenetic approaches

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