Concordance between semen‐derived HIV‐1 proviral DNA and viral RNA hypervariable region 3 (V3) envelope sequences in cases where semen populations are distinct from those present in blood

Curran, Rebecca; Ball, Jonathan K.

doi:10.1002/jmv.2186

Cited by 20 publications

(23 citation statements)

References 60 publications

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“…Table 1 summarizes the patient material that was used in this study. Semen-and bloodderived envelopes were from three adults at different disease stages (9). Pediatric-derived envelopes were from plasma taken from early and late disease stages of three patients.…”

Section: Methodsmentioning

confidence: 99%

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Non-Macrophage-Tropic Human Immunodeficiency Virus Type 1 R5 Envelopes Predominate in Blood, Lymph Nodes, and Semen: Implications for Transmission and Pathogenesis

Peters

Sullivan

Dueñas-Decamp

et al. 2006

J Virol

188

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Human immunodeficiency virus type 1 (HIV-1) R5 isolates that predominantly use CCR5 as a coreceptor are frequently described as macrophage tropic. Here, we compare macrophage tropism conferred by HIV-1 R5 envelopes that were derived directly by PCR from patient tissue. This approach avoids potentially selective culture protocols used in virus isolation. Envelopes were amplified (i) from blood and semen of adult patients and (ii) from plasma of pediatric patients. The phenotypes of these envelopes were compared to those conferred by an extended panel of envelopes derived from brain and lymph node that we reported previously. Our results show that R5 envelopes vary by up to 1,000-fold in their capacity to confer infection of primary macrophages. Highly macrophage-tropic envelopes were predominate in brain but were infrequent in semen, blood, and lymph node samples. We also confirmed that the presence of N283 in the C2 CD4 binding site of gp120 is associated with HIV-1 envelopes from the brain but absent from macrophage-tropic envelopes amplified from blood and semen. Finally, we compared infection of macrophages, CD4 ؉ T cells, and peripheral blood mononuclear cells (PBMCs) conferred by macrophage-tropic and non-macrophage-tropic envelopes in the context of full-length replication competent viral clones. Non-macrophage-tropic envelopes conferred low-level infection of macrophages yet infected CD4؉ T cells and PBMCs as efficiently as highly macrophage-tropic brain envelopes. The lack of macrophage tropism for the majority of the envelopes amplified from lymph node, blood, and semen is striking and contrasts with the current consensus that R5 primary isolates are generally macrophage tropic. The extensive variation in R5 tropism reported here is likely to have an important impact on pathogenesis and on the capacity of HIV-1 to transmit.

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Section: Methodsmentioning

confidence: 99%

“…Envelopes from P3, P31 and P43 were amplified by limiting dilution from proviral DNA from semen and blood cells (9). Similar procedures were followed to amplify envelopes from pediatric HIV-1 RNA in plasma following synthesis of envelope cDNA using SuperScript reverse transcriptase (RT; Invitrogen Inc.).…”

Section: Methodsmentioning

confidence: 99%

Non-Macrophage-Tropic Human Immunodeficiency Virus Type 1 R5 Envelopes Predominate in Blood, Lymph Nodes, and Semen: Implications for Transmission and Pathogenesis

Peters

Sullivan

Dueñas-Decamp

et al. 2006

J Virol

188

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“…The inherent genetic variability of the population leads to humoral (86) and cellular (31) immune escape, resistance to antiretrovirals (9), and altered cytopathogenicity and cell tropism (48)(49)(50). Compartmentalization of HIV-1 populations derived from a range of tissues has been reported, including blood versus brain/central nervous system (1,27,47,53,67), brain versus lymph (4,42,68), blood versus female genital tract (51), and blood versus semen (10,12,24,52,93). In addition, genetic segregation of HIV-1 variants is also apparent between different populations of Langerhans cells (61) and at different sites within the brain (63), spleen (11), and gut (79).…”

mentioning

confidence: 99%

Intercompartmental Recombination of HIV-1 Contributes toenvIntrahost Diversity and Modulates Viral Tropism and Sensitivity to Entry Inhibitors

Brown

Peters

Caron

et al. 2011

J Virol

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HIV-1 circulates within an infected host as a genetically heterogeneous viral population. Viral intrahost diversity is shaped by substitutional evolution and recombination. Although many studies have speculated that recombination could have a significant impact on viral phenotype, this has never been definitively demonstrated. We report here phylogenetic and subsequent phenotypic analyses of envelope genes obtained from HIV-1 populations present in different anatomical compartments. Assessment of env compartmentalization from immunologically discrete tissues was assessed utilizing a single genome amplification approach, minimizing in vitro-generated artifacts. Genetic compartmentalization of variants was frequently observed. In addition, multiple incidences of intercompartment recombination, presumably facilitated by low-level migration of virus or infected cells between different anatomic sites and coinfection of susceptible cells by genetically divergent strains, were identified. These analyses demonstrate that intercompartment recombination is a fundamental evolutionary mechanism that helps to shape HIV-1 env intrahost diversity in natural infection. Analysis of the phenotypic consequences of these recombination events showed that genetic compartmentalization often correlates with phenotypic compartmentalization and that intercompartment recombination results in phenotype modulation. This represents definitive proof that recombination can generate novel combinations of phenotypic traits which differ subtly from those of parental strains, an important phenomenon that may have an impact on antiviral therapy and contribute to HIV-1 persistence in vivo.

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“…Various organs are already infected at this early stage (Zhang et al 2002), and assessing how viruses from these organs evolve should help to understand AIDS progression and HIV-1 pathogenesis. A possible scenario is that viruses from different organs could diverge and evolve separately.As an example of this scenario, HIV-1 populations infecting blood and semen show different biological properties (Coombs et al 1998) and are sometimes compartmentalized (Zhu et al 1996;Delwart et al 1998;Curran and Ball 2002). Similarly, variants are unevenly distributed in cervical swabs and blood (Poss et al 1995), but are rarely restricted to one of them (Sankale et al 1998;Shaheen et al 1999).…”

mentioning

confidence: 99%

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

et al. 2004

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Abstract. The existence of organ-specific HIV-1 populations within infected hosts has been studied for many years; nonetheless results reported by different authors are somewhat discrepant. To tackle this problem, we used a population genetics approach to analyze previously published data from the V3 hypervariable region of the envelope env gene. Our results are compatible with a population subdivision by organs in 95% of individuals analyzed at autopsy. In addition, populations infecting the nervous system and testicles clearly appear as differentiated subsets of the socalled macrophage-tropic variants. Liver and kidney may harbor differentiated populations as well. Although it is widely accepted that organ compartmentalization arises as a consequence of different selective pressures imposed by different organs, a definitive demonstration has not yet been provided. Our analysis of the pattern of synonymous and nonsynonymous nucleotide substitutions provides evidence supporting this hypothesis, without discarding the role of other evolutionary processes. In contrast, positive selection does not seem to be the mechanism responsible for the evolution of patient-specific sequences.Key words. Adaptation, gene flow, metapopulations, organ-driven selection, viral dynamics, viral evolution.Received October 6, 2003. Accepted January 19, 2004 It has been well established that human immunodeficiency virus type 1 (HIV-1) infections begin with a homogeneous population (Karlsson et al. 1998;Zhang et al. 2002), but during the initial acute stage of the disease diversity rapidly rises (McNearney et al. 1992;Pang et al. 1992;Poss et al. 1995) and keeps growing during the nonsymptomatic stage of the disease (Keys et al. 1993). Various organs are already infected at this early stage (Zhang et al. 2002), and assessing how viruses from these organs evolve should help to understand AIDS progression and HIV-1 pathogenesis. A possible scenario is that viruses from different organs could diverge and evolve separately.As an example of this scenario, HIV-1 populations infecting blood and semen show different biological properties (Coombs et al. 1998) and are sometimes compartmentalized (Zhu et al. 1996;Delwart et al. 1998;Curran and Ball 2002). Similarly, variants are unevenly distributed in cervical swabs and blood (Poss et al. 1995), but are rarely restricted to one of them (Sankale et al. 1998;Shaheen et al. 1999). Viruses from blood and lung have also been shown to evolve separately (Itescu et al. 1994), though this seems not to be the norm for all patients studied (Collins et al. 2002). An alternative scenario is that all body sites harbor a common viral pool of which blood-circulating samples are representative. Supporting this possibility, several authors found no compelling evidence for organ-structure in lung, lymphatic nodes, testicles, spleen, kidney or even bone marrow (Ball et al. 1994;van't Wout et al. 1998), between colon and blood (van der Hoek et al. 1998), or between thymus and lymphatic nodes (Alves et al. 2002). Virus...

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Concordance between semen‐derived HIV‐1 proviral DNA and viral RNA hypervariable region 3 (V3) envelope sequences in cases where semen populations are distinct from those present in blood

Cited by 20 publications

References 60 publications

Non-Macrophage-Tropic Human Immunodeficiency Virus Type 1 R5 Envelopes Predominate in Blood, Lymph Nodes, and Semen: Implications for Transmission and Pathogenesis

Non-Macrophage-Tropic Human Immunodeficiency Virus Type 1 R5 Envelopes Predominate in Blood, Lymph Nodes, and Semen: Implications for Transmission and Pathogenesis

Intercompartmental Recombination of HIV-1 Contributes toenvIntrahost Diversity and Modulates Viral Tropism and Sensitivity to Entry Inhibitors

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

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