Enhanced cellular responses and environmental sampling within inner foreskin explants: implications for the foreskin's role in HIV transmission

Fahrbach, Kelly M.; Barry, Sheila M.; Anderson, Meegan R.; Hope, Thomas J.

doi:10.1038/mi.2010.18

Cited by 47 publications

(52 citation statements)

References 31 publications

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“…DCs have been proposed to play an important role in HIV-1 transmission, because they are located in the mucosa (39,40), capture viruses using lectins (41,42) and glycosphingolipid receptors (43), and efficiently transmit infectious particles to CD4+ T cells (44)(45)(46). To examine whether TF and CC viruses differ in their ability to bind DCs, we pulsed immature monocyte-derived DCs (moDCs) with equal amounts of virus (normalized by RT activity), washed the cells extensively to remove cell-free virions, and then lysed the cells to quantify the amount of cell-associated virus.…”

Section: Resultsmentioning

confidence: 99%

Phenotypic properties of transmitted founder HIV-1

Parrish

Gao

Li³

et al. 2013

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

374

432

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Defining the virus-host interactions responsible for HIV-1 transmission, including the phenotypic requirements of viruses capable of establishing de novo infections, could be important for AIDS vaccine development. Previous analyses have failed to identify phenotypic properties other than chemokine receptor 5 (CCR5) and CD4+ T-cell tropism that are preferentially associated with viral transmission. However, most of these studies were limited to examining envelope (Env) function in the context of pseudoviruses. Here, we generated infectious molecular clones of transmitted founder (TF; n = 27) and chronic control (CC; n = 14) viruses of subtypes B (n = 18) and C (n = 23) and compared their phenotypic properties in assays specifically designed to probe the earliest stages of HIV-1 infection. We found that TF virions were 1.7-fold more infectious (P = 0.049) and contained 1.9-fold more Env per particle (P = 0.048) compared with CC viruses. TF viruses were also captured by monocyte-derived dendritic cells 1.7-fold more efficiently (P = 0.035) and more readily transferred to CD4+ T cells (P = 0.025). In primary CD4+ T cells, TF and CC viruses replicated with comparable kinetics; however, when propagated in the presence of IFN-α, TF viruses replicated to higher titers than CC viruses. This difference was significant for subtype B (P = 0.000013) but not subtype C (P = 0.53) viruses, possibly reflecting demographic differences of the respective patient cohorts. Together, these data indicate that TF viruses are enriched for higher Env content, enhanced cell-free infectivity, improved dendritic cell interaction, and relative IFN-α resistance. These viral properties, which likely act in concert, should be considered in the development and testing of AIDS vaccines.

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Section: Resultsmentioning

confidence: 99%

Phenotypic properties of transmitted founder HIV-1

Parrish

Gao

Li³

et al. 2013

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

374

432

View full text Add to dashboard Cite

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“…Most studies have focused on transmission across the female genital mucosa, whereas mechanisms of HIV transmission across penile tissue are much less well understood, and are subject to ongoing research [11][12][13][14][15][16][17][18][19].…”

Section: Reviews In Medical Virologymentioning

confidence: 99%

HIV sexual transmission and microbicides

Ariën

Jespers

Vanham

2011

Reviews in Medical Virology

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Pathogens often rely on the contacts between hosts for transmission. Most viruses have adapted their transmission mechanisms to defined behaviours of their host(s) and have learned to exploit these for their own propagation. Some viruses, such as HIV, the human papillomavirus (HPV), HSV-2 and HCV, cause sexually transmitted infections (STIs). Understanding the transmission of particular viral variants and comprehending the early adaptation and evolution is fundamental to eventually inhibiting sexual transmission of HIV. Here, we review the current understanding of the mechanisms of sexual transmission and the biology of the transmitted HIV. Next, we present a timely overview of candidate microbicides, including past, ongoing and future clinical trials of HIV topical microbicides.

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“…Sexual HIV transmission is an inefficient process during which a limited number of virions initiate an infection in a new host, resulting in a severe transmission bottleneck [15,16]. Although CD4 + T cells are the predominant target cells of HIV, it has been postulated that dendritic cells (DCs) naturally residing in the genital mucosa play a major role during sexual transmission [17][18][19][20]. Within the genital mucosa, Langerhans cells (LCs) reside in the epithelial layer and are the first DC subset encountered by HIV.…”

Section: Introductionmentioning

confidence: 99%

Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model

et al. 2014

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Background: Different patterns of drug resistance are observed in treated and therapy naïve HIV-1 infected populations. Especially the NRTI-related M184I/V variants, which are among the most frequently encountered mutations in treated patients, are underrepresented in the antiretroviral naïve population. M184I/V mutations are known to have a profound effect on viral replication and tend to revert over time in the new host. However it is debated whether a diminished transmission efficacy of HIV variants with a reduced replication capacity can also contribute to the observed discrepancy in genotypic patterns. As dendritic cells (DCs) play a pivotal role in HIV-1 transmission, we used a model containing primary human Langerhans cells (LCs) and DCs to compare the transmission efficacy M184 variants (HIV-M184V/I/T) to HIV wild type (HIV-WT). As control, we used HIV harboring the NNRTI mutation K103N (HIV-K103N) which has a minor effect on replication and is found at a similar prevalence in treated and untreated individuals.

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Enhanced cellular responses and environmental sampling within inner foreskin explants: implications for the foreskin's role in HIV transmission

Cited by 47 publications

References 31 publications

Phenotypic properties of transmitted founder HIV-1

Phenotypic properties of transmitted founder HIV-1

HIV sexual transmission and microbicides

Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model

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