Differential Transmission of HIV Traversing Fetal Oral/Intestinal Epithelia and Adult Oral Epithelia

Tugizov, Sharof M.; Herrera, Rossana; Veluppillai, Piri; Greenspan, Deborah; Soros, Vanessa B.; Greene, Warner C.; Levy, Jay A.; Palefsky, Joel M.

doi:10.1128/jvi.06578-11

Cited by 63 publications

(94 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1,2,42,43 HIV-infected macrophages were shown to transmigrate via fetal oral mucosa 44 without disrupting the epithelial TJs. The results from the present study suggest that HIV transmission through the ectocervical and colon mucosa may occur via unidentified mechanism without TJ/AJ disruption.…”

Section: Discussionmentioning

confidence: 99%

HIV Exposure to the Epithelia in Ectocervical and Colon Tissues Induces Inflammatory Cytokines Without Tight Junction Disruption

Sankapal

Gupta

Ratner

et al. 2016

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

Epithelial cells in human cervical and colonic mucosa do not express HIV receptor. However, HIV transmission occurs across the unbreached epithelia by an unknown mechanism. In this study, the effect of HIV exposure on tight junction (TJ) and cytokine production in ectocervical and colon mucosal epithelia in tissue biopsies was investigated in an organ culture model. After HIV exposure, the distribution patterns and quantities of epithelial TJ and adherens proteins were evaluated by immunofluorescence staining followed by confocal microscopy. Cytokine mRNA in the mucosal epithelia was also evaluated by real-time reverse transcription-polymerase chain reaction (RT-PCR). HIV transmission was evaluated by measuring p24 production in culture supernatant. Our results showed there were no significant changes in the distribution and quantities of epithelial TJ/adherens junction (AJ) proteins after exposure to HIV. However, higher levels of CXCL10 and CXCL11 mRNA expression were detected in HIV-exposed ectocervical epithelia. In case of colon mucosa, higher levels of CXCL10 and IL-6 mRNA expression were detected in HIV-exposed colon mucosa. Our study suggests that HIV induces cytokine production in epithelial cells, which may facilitate HIV transmission by recruiting HIV target cells in the submucosal region. Furthermore, HIV transmission may not occur through epithelial TJ/AJ disruption.

show abstract

Section: Discussionmentioning

confidence: 99%

HIV Exposure to the Epithelia in Ectocervical and Colon Tissues Induces Inflammatory Cytokines Without Tight Junction Disruption

Sankapal

Gupta

Ratner

et al. 2016

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

show abstract

“…It has been shown that stratified mucosal epithelia, including the oral mucosal epithelium, have well-developed tight junctions (34)(35)(36)(37), which initiate development of the distinct polarized apical and basolateral membranes of epithelial cells (38,39). The polarization of epithelial cells determines the pathways of viral entry and egress (18,(39)(40)(41)(42)(43)(44)(45)(46)(47)(48).…”

Section: Pstein-barr Virus (Ebv) Is An Oncogenic Human Herpesvirus Camentioning

confidence: 99%

“…It is well documented that polarized tonsil, endometrial, liver, placental, kidney, and intestinal epithelial cells facilitate rapid transcellular transcytosis of various human viruses, including human immunodeficiency virus (HIV), human cytomegalovirus (HCMV), influenza virus, and poliovirus (38,39,(51)(52)(53)(54)(55)(56)(57)(58)(59). Transcytosis of viruses may occur bidirectionally (41,60), i.e., from both the apical to the basolateral membranes and the basolateral to the apical membranes, and do so by the following sequential steps: (i) endocytosis of virions into early endosomal and sorting vesicles, (ii) sorting and delivery of virions to basolateral (or apical) vesicles, and (iii) release of virions from the basolateral (or apical) membranes.…”

Section: Pstein-barr Virus (Ebv) Is An Oncogenic Human Herpesvirus Camentioning

confidence: 99%

See 1 more Smart Citation

Epstein-Barr Virus Transcytosis through Polarized Oral Epithelial Cells

Tugizov

Herrera

Palefsky

2013

J Virol

Self Cite

View full text Add to dashboard Cite

Although Epstein-Barr virus (EBV) is an orally transmitted virus, viral transmission through the oropharyngeal mucosal epithelium is not well understood. In this study, we investigated how EBV traverses polarized human oral epithelial cells without causing productive infection. We found that EBV may be transcytosed through oral epithelial cells bidirectionally, from both the apical to the basolateral membranes and the basolateral to the apical membranes. Apical to basolateral EBV transcytosis was substantially reduced by amiloride, an inhibitor of macropinocytosis. Electron microscopy showed that virions were surrounded by apical surface protrusions and that virus was present in subapical vesicles. Inactivation of signaling molecules critical for macropinocytosis, including phosphatidylinositol 3-kinases, myosin light-chain kinase, Ras-related C3 botulinum toxin substrate 1, p21-activated kinase 1, ADP-ribosylation factor 6, and cell division control protein 42 homolog, led to significant reduction in EBV apical to basolateral transcytosis. In contrast, basolateral to apical EBV transcytosis was substantially reduced by nystatin, an inhibitor of caveolin-mediated virus entry. Caveolae were detected in the basolateral membranes of polarized human oral epithelial cells, and virions were detected in caveosome-like endosomes. Methyl ␤-cyclodextrin, an inhibitor of caveola formation, reduced EBV basolateral entry. EBV virions transcytosed in either direction were able to infect B lymphocytes. Together, these data show that EBV transmigrates across oral epithelial cells by (i) apical to basolateral transcytosis, potentially contributing to initial EBV penetration that leads to systemic infection, and (ii) basolateral to apical transcytosis, which may enable EBV secretion into saliva in EBV-infected individuals.

show abstract

“…However, in comparison to adults, the oral mucosa of infants is incompletely stratified and contains lower levels of innate anti-HIV factors rendering it much more susceptible to HIV infection. 42,43 Our results showing strong in vitro HIV inhibitory activity in serum, CVS and saliva after a single oral dose of 4 ′ -ethynyl-2-fluoro-2 ′ -deoxyadenosine demonstrates efficient penetration of active 4 ′ -ethynyl-2-fluoro-2 ′ -deoxyadenosine into highly relevant mucosal sites of transmission following a vaginal or oral HIV challenge. Even after a 20-fold dilution, the CVS and saliva of 4 ′ -ethynyl-2-fluoro-2 ′ -deoxyadenosine-treated animals significantly inhibited HIV infection in vitro (50% inhibition CVS, 90% inhibition saliva).…”

Section: Discussionmentioning

confidence: 81%

HIV pre-exposure prophylaxis for women and infants prevents vaginal and oral HIV transmission in a preclinical model of HIV infection

Kovářová

Shanmugasundaram

Baker

et al. 2016

J. Antimicrob. Chemother.

View full text Add to dashboard Cite

Differential Transmission of HIV Traversing Fetal Oral/Intestinal Epithelia and Adult Oral Epithelia

Cited by 63 publications

References 62 publications

HIV Exposure to the Epithelia in Ectocervical and Colon Tissues Induces Inflammatory Cytokines Without Tight Junction Disruption

HIV Exposure to the Epithelia in Ectocervical and Colon Tissues Induces Inflammatory Cytokines Without Tight Junction Disruption

Epstein-Barr Virus Transcytosis through Polarized Oral Epithelial Cells

HIV pre-exposure prophylaxis for women and infants prevents vaginal and oral HIV transmission in a preclinical model of HIV infection

Contact Info

Product

Resources

About