Early events in HIV transmission through a human reconstructed vaginal mucosa

Bouschbacher, Marielle; Bomsel, Morgane; Verronèse, Estelle; Gofflo, Sandrine; Ganor, Yonatan; Dezutter‐Dambuyant, Colette; Valladeau, Jenny

doi:10.1097/qad.0b013e3282f736f4

Cited by 51 publications

(37 citation statements)

References 40 publications

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“…57 In contrast, a recent study was unable to detect translocation of HIV-1 in reconstructed human vaginal mucosa, and presence of Langerhans cells did not alter HIV-1 transmission. 58 These studies suggest that the main target cells for HIV-1 are CD4 + DCs and T cells in the lamina propria of genital mucosa. Consequently, the enriched population of CD4 + T cells and APCs present in the transformation zone, where the ectocervix transitions into the endocervix, may be a particularly susceptible site for HIV entry.…”

Section: Hiv Interactions With Epithelial Barrier and Target Cells Inmentioning

confidence: 99%

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

Kaushic

Ferreira

Kafka

et al. 2010

American J Rep Immunol

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Citation Kaushic C, Ferreira VH, Kafka JK, Nazli A. HIV infection in the female genital tract: discrete influence of the local mucosal microenvironment. Am J Reprod Immunol 2010Women acquire HIV infections predominantly at the genital mucosa through heterosexual transmission. Therefore, the immune milieu at female genital surfaces is a critical determinant of HIV susceptibility. In this review, we recapitulate the evidence suggesting that several distinctive innate immune mechanisms in the female genital tract (FGT) serve to significantly deter or facilitate HIV‐1 infection. Epithelial cells lining the FGT play a key role in forming a primary barrier to HIV entry. These cells express Toll‐like receptors and other receptors that recognize and respond directly to pathogens, including HIV‐1. In addition, innate biological factors produced by epithelial and other cells in the FGT have anti‐HIV activity. Female sex hormones, co‐infection with other pathogens and components in semen may also exacerbate or down‐modulate HIV transmission. A combination of innate and adaptive immune factors and their interactions with the local microenvironment determine the outcome of HIV transmission. Improving our understanding of the female genital microenvironment will be useful in developing treatments that augment and sustain protective immune responses in the genital mucosa, such as microbicides and vaccines, and will provide greater insight into viral pathogenesis in the FGT.

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Section: Hiv Interactions With Epithelial Barrier and Target Cells Inmentioning

confidence: 99%

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

Kaushic

Ferreira

Kafka

et al. 2010

American J Rep Immunol

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“…The mechanism of HIV transmission across the mucosa still remains an unresolved enigma, despite outstanding studies that have already shed light on relevant issues (Bomsel, 1997;Bouschbacher et al, 2008;Collins et al, 2000;Gupta et al, 2002;Hladik et al, 2007;Hu et al, 2000;Kawamura et al, 2000;Spira et al, 1996;Tan & Phillips, 1996;Zhang et al, 1999). In particular, two cell types are considered targets of HIV infection at the port of entry, i.e.…”

Section: Introductionmentioning

confidence: 99%

Human immunodeficiency virus type 1 (HIV-1) protease inhibitors block cell-to-cell HIV-1 endocytosis in dendritic cells

Muratori

Ruggiero

Sistigu

et al. 2009

Journal of General Virology

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Sexual transmission is now the most frequent means of diffusion of human immunodeficiency virus type 1 (HIV-1). Even if the underlying mechanism is still largely unknown, there is a consensus regarding the key role played by mucosal dendritic cells (DCs) in capturing HIV through contact with infected subepithelial lymphocytes, and their capacity to spread HIV by trans-infection. We found that HIV protease inhibitors (PIs) reduced virion endocytosis strongly in monocyte-derived immature (i) DCs contacting HIV-1-infected cells, and that this phenomenon led to dramatically impaired trans-infection activity. This inhibitory effect was not mediated by the block of viral protease activity, as it was also operative when donor cells were infected with a PI-resistant HIV-1 strain. The block of virus maturation imposed by PIs did not correlate with significant variations in the levels of virus expression in donor cells or of Gag/Env virion incorporation. Also, PIs did not affect the endocytosis activity of DCs. In contrast, we noticed that PI treatment inhibited the formation of cell-cell conjugates whilst reducing the expression of ICAM-1 in target iDCs. Our results contribute to a better delineation of the mechanisms underlying HIV-1 trans-infection activity in DCs, whilst having implications for the development of new anti-HIV microbicide strategies.

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“…Previous studies using kidney cell cultures suggested that paracellular permeability to electrical currents and non-charged solutes may be regulated by different sets of tight junctional proteins. [39][40][41][42][43] If this is the case, given that multiple types of tight junctional proteins are expressed in human cervicovaginal mucosa, 9,[44][45][46] it is possible that EDTA treatment affected certain tight junction proteins that control small-molecule movement, but it did not affect those that control electrical current flux. Such a change in the organization of tight junction, in our opinion, is not comparable to the physical breaches that facilitate HIV-1 entry into the submucosal compartment, [47][48][49] due to the difference in size and the entry mechanism between HIV-1 and mannitol.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Commonly Used Excipients on the Epithelial Integrity of Human Cervicovaginal Tissue

Zhou

Dezzutti

et al. 2016

AIDS Research and Human Retroviruses

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Pharmaceutical excipients are widely used in vaginal drug products. The epithelial integrity of the cervicovaginal tissue is important for HIV-1 prevention. However, the effects of excipients on cervicovaginal epithelium remain unknown. This study aims at assessing the effects of vaginal product excipients on the integrity of human cervicovaginal epithelium and on a lead HIV prevention antiretroviral drug, tenofovir (TFV). In the current study, nine excipients commonly used in vaginal formulations were incubated for 6 h with excised human ectocervical tissue. The effects of the excipients were examined by measuring the transepithelial electrical resistance (TEER), epithelial morphology, paracellular/transcellular permeability, and cell viability. The efficacy of TFV for preventing HIV-1 infection in the ex vivo cultured ectocervix was also tested. We found that disodium ethyl-enediaminetetraacetate (EDTA), sorbic acid, and benzoic acid had no effect on the tissue TEER. Butylated hydroxyanisole, glycerin, propylene glycol, methylparaben, and propylparaben slightly to moderately decreased tissue TEER, whereas citric acid significantly decreased the TEER in a time-dependent manner. Tissue morphology observed post-exposure strongly correlated with TEER data; however, a less strong correlation was observed between paracellular permeability and TEER data after exposure to different excipients. In addition, treatment with EDTA, methylparaben, and propylene glycol at tested levels had no effect on the efficacy of TFV in preventing tissue HIV-1 infection. In conclusion, the combined measurements of TEER, morphology, permeability, and viability using human cervicovaginal tissue represent a clinically relevant platform for safety evaluation of excipients and formulated products for HIV-1 prevention.

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Early events in HIV transmission through a human reconstructed vaginal mucosa

Cited by 51 publications

References 40 publications

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

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

Human immunodeficiency virus type 1 (HIV-1) protease inhibitors block cell-to-cell HIV-1 endocytosis in dendritic cells

The Effect of Commonly Used Excipients on the Epithelial Integrity of Human Cervicovaginal Tissue

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