REVIEW ARTICLE: HIV Infection in the Female Genital Tract: Discrete Influence of the Local Mucosal Microenvironment

Kaushic, Charu; Ferreira, Victor H; Kafka, Jessica K.; Nazli, Aisha

doi:10.1111/j.1600-0897.2010.00843.x

Cited by 41 publications

(34 citation statements)

References 100 publications

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“…These include secretory leukocyte protease inhibitor (SLPI), a-and b-defensins as well as trappin-2/elafin. 13 More recently, antiproteases, such as serpins and cystatins expressed by GECs, have also been shown to inhibit HIV binding and replication and reduce local inflammation. 14 In addition to AMPs, cells of the FGT can produce interferons (IFNs) that have a wide variety of immunomodulatory and antiviral effects.…”

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confidence: 99%

Influence of Common Mucosal Co‐Factors on HIV Infection in the Female Genital Tract

Ferreira

Kafka

Kaushic

2014

American J Rep Immunol

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confidence: 99%

Influence of Common Mucosal Co‐Factors on HIV Infection in the Female Genital Tract

Ferreira

Kafka

Kaushic

2014

American J Rep Immunol

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“…18). Increased levels of genital tract proinflammatory cytokines can promote viral replication in the mucosa and thereby recruit immune target cells leading to increased HIV shedding (19)(20)(21).…”

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confidence: 99%

Stable CD4 Expression and Local Immune Activation in the Ectocervical Mucosa of HIV-Infected Women

Hirbod

Kimani

Tjernlund

et al. 2013

The Journal of Immunology

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Studies using genital tissue samples from HIV-infected women might provide important information about HIV susceptibility and transmission. In this study, ectocervical biopsies were obtained from 20 HIV-seropositive (HIV+) Kenyan female sex workers (FSW) and 20 HIV-seronegative lower risk (HIV− LR) women. To control for the impact of sex work, 20 HIV− FSW were also recruited. Immune molecules were assessed in situ by immunohistochemistry and for mRNA expression by quantitative PCR. The HIV+ women were reportedly infected for a median of 3 y (1–21 y), with a median viral load of 11,735 copies/ml (20–648,000 copies/ml). These women had significantly lower CD4 blood cell counts than the HIV− LR women but comparable levels of CD4 expression in ectocervix. Whereas cellular markers were similar between the HIV+ group and the HIV− LR women, the HIV-binding molecules CCR5, dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin, and mannose receptor as well as the inflammatory markers CD69, IFN-γ, IL-6, and IL-22 were significantly upregulated in the HIV+ group. As compared with the HIV− FSW women, the HIV+ women had significantly upregulated levels of CD4, CD3, CCR5, Langerin, dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin, and mannose receptor as well as inflammatory cytokines. The CD4 cell depletion previously seen in the gut mucosa of HIV-infected individuals was thus not observed in the ectocervical mucosa. Stable CD4 cell expression and local immune activation in the lower female genital tract may promote viral replication and genital shedding and increase the risk of sexual HIV transmission.

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“…Indeed, the vaginal and cervical epithelium have been shown to be transiently infectable by HIV-1 and most likely play a role in transporting the virus to target local T cells, resulting in productive systemic viral infection [6,30,31]. This is also the surface targeted for microbicide therapeutics [32][33][34][35][36].…”

Section: Fsl-gb 3 Inhibits Hiv-1 Iiib Infection Of Human Endometrial mentioning

confidence: 96%

A Novel VSV/HIV Pseudotype Approach for the Study of HIV Microbicides Without Requirement for level 3 Biocontainment

Harrison

Henry

Mahfoud³

et al. 2011

Future Virol.

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Studies of potential HIV mucosal microbicides are difficult to undertake due to the requirement for a suitable animal model and the use of biosafety level 3 containment, which are not always available to researchers. Here we show the use of a mouse model of vaginal and rectal transmission of an HIV chimeric virus that does not require level 3 biosafety containment, to test the ex vivo efficacy of soluble Gb3 analogs for the prevention of mucosal HIV infection. The model uses a pseudoenvelope-typed vesicular stomatitis virus (VSV)/HIV recombinant virus that can infect all murine cell types. We demonstrate that the envelope glycoproteins VSV-G of VSV and gp-120 of HIV both bind Gb3. We show that soluble Gb3 analogs inhibit in vitro infection of cervical and vaginal-derived cell lines by both intact HIV and the VSV/HIV recombinant virus. Soluble Gb3 analogs incorporated into gel or used alone and applied directly to the vaginal and rectal mucosal tissue of mice were able to resist viral infection as monitored by PCR and quantitative real-time PCR copy number of HIV cDNA extracted from mouse tissue. Only a trend towards significant efficacy for prevention of mucosal transmission through lower copy number in the treatment groups was evident from these studies; however, this finding warrants further evaluation. In addition, we illustrate a methodology to evaluate inflammatory responses in either vagina or rectum after administration of soluble microbicidal compounds. These studies provide a potential new ex vivo methodology suitable for animal facilities in general, to screen microbicide drug candidates, including drug candidates that target viral proteins, for efficacy and safety, in order to accelerate development and discovery of prophylactic and therapeutic agents for HIV/AIDS.

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REVIEW ARTICLE: HIV Infection in the Female Genital Tract: Discrete Influence of the Local Mucosal Microenvironment

Cited by 41 publications

References 100 publications

Influence of Common Mucosal Co‐Factors on HIV Infection in the Female Genital Tract

Influence of Common Mucosal Co‐Factors on HIV Infection in the Female Genital Tract

Stable CD4 Expression and Local Immune Activation in the Ectocervical Mucosa of HIV-Infected Women

A Novel VSV/HIV Pseudotype Approach for the Study of HIV Microbicides Without Requirement for level 3 Biocontainment

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