Natural Selection and the Organ-Specific Differentiation of Hiv-1 V3 Hypervariable Region

Sanjuán, Rafael; Codoñer, Francisco M.; Moya, Andrés; Elena, Santiago F.

doi:10.1554/03-577

Cited by 15 publications

(15 citation statements)

References 57 publications

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“…3 Anatomical compartments representing discrete sites of independent viral evolution include the central nervous system, genital tract, kidney epithelium, and lymph nodes. [10][11][12][13][14] Whether the same is true within TB coinfected granulomas is currently unclear and inconclusive. [15][16][17] Understanding the dynamics of viral evolution within this unique highly compartmentalized but immunologically active environment is important to virus eradication strategies.…”

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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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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“…Instead, the metapopulation concept, where a population is made up of several discrete subpopulations that undergo turnover through frequent foundation and extinction events, could play a central role in the evolution of HIV-1 (17). Differentiation of subpopulations in various organs of the same host has been further confirmed more recently for HIV (24,30,33,37) and has also been reported for other animal virus species such as Hepatitis C virus (1,9,25) and TT virus (29).…”

mentioning

confidence: 95%

Distinct Viral Populations Differentiate and Evolve Independently in a Single Perennial Host Plant

Jridi

Martin

Marie-Jeanne

et al. 2006

J Virol

116

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The complex structure of virus populations has been the object of intensive study in bacteria, animals, and plants for over a decade. While it is clear that tremendous genetic diversity is rapidly generated during viral replication, the distribution of this diversity within a single host remains an obscure area in this field of science. Among animal viruses, only Human immunodeficiency virus and Hepatitis C virus populations have recently been thoroughly investigated at an intrahost level, where they are structured as metapopulations, demonstrating that the host cannot be considered simply as a "bag" containing a homogeneous or unstructured swarm of mutant viral genomes. In plants, a few reports suggested a possible heterogeneous distribution of virus variants at different locations within the host but provided no clues as to how this heterogeneity is structured. Here, we report the most exhaustive study of the structure and evolution of a virus population ever reported at the intrahost level through the analysis of a Prunus tree infected by Plum pox virus for over 13 years following a single inoculation event and by using analysis of molecular variance at different hierarchical levels combined with nested clade analysis. We demonstrate that, following systemic invasion of the host, the virus population differentiates into several distinct populations that are isolated in different branches, where they evolve independently through contiguous range expansion while colonizing newly formed organs. Moreover, we present and discuss evidence that the tree harbors a huge "bank" of viral clones, each isolated in one of the myriad leaves.

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“…Sophisticated genetic tests can detect such population structure in a sample of viral sequences (4,39,49). Using two complementary tests of population structure (14,43), we analyzed viral sequences from multiple sources within individual patients in order to determine whether a source other than circulating resting CD4 ϩ T cells contributes to residual viremia and viral persistence.…”

mentioning

confidence: 99%

“…The second test of population structure involved the analysis of molecular variance (AMOVA) (4,14,39). This test is implemented in the software package Arlequin (2).…”

mentioning

confidence: 99%

Analysis of Human Immunodeficiency Virus Type 1 Viremia and Provirus in Resting CD4 ⁺ T Cells Reveals a Novel Source of Residual Viremia in Patients on Antiretroviral Therapy

Brennan

Woods

Sedaghat

et al. 2009

J Virol

120

108

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Highly active antiretroviral therapy (HAART) can reduce human immunodeficiency virus type 1 (HIV-1) viremia to clinically undetectable levels. Despite this dramatic reduction, some virus is present in the blood. In addition, a long-lived latent reservoir for HIV-1 exists in resting memory CD4 ؉ T cells. This reservoir is believed to be a source of the residual viremia and is the focus of eradication efforts. Here, we use two measures of population structure-analysis of molecular variance and the Slatkin-Maddison test-to demonstrate that the residual viremia is genetically distinct from proviruses in resting CD4؉ T cells but that proviruses in resting and activated CD4 ؉ T cells belong to a single population. Residual viremia is genetically distinct from proviruses in activated CD4؉ T cells, monocytes, and unfractionated peripheral blood mononuclear cells. The finding that some of the residual viremia in patients on HAART stems from an unidentified cellular source other than CD4 ؉ T cells has implications for eradication efforts.

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Natural Selection and the Organ-Specific Differentiation of Hiv-1 V3 Hypervariable Region

Cited by 15 publications

References 57 publications

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

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

Distinct Viral Populations Differentiate and Evolve Independently in a Single Perennial Host Plant

Analysis of Human Immunodeficiency Virus Type 1 Viremia and Provirus in Resting CD4 ⁺ T Cells Reveals a Novel Source of Residual Viremia in Patients on Antiretroviral Therapy

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Natural Selection and the Organ-Specific Differentiation of Hiv-1 V3 Hypervariable Region

Cited by 15 publications

References 57 publications

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

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

Distinct Viral Populations Differentiate and Evolve Independently in a Single Perennial Host Plant

Analysis of Human Immunodeficiency Virus Type 1 Viremia and Provirus in Resting CD4 + T Cells Reveals a Novel Source of Residual Viremia in Patients on Antiretroviral Therapy

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Analysis of Human Immunodeficiency Virus Type 1 Viremia and Provirus in Resting CD4 ⁺ T Cells Reveals a Novel Source of Residual Viremia in Patients on Antiretroviral Therapy