Human Immunodeficiency Virus Type 1 Infection and Replication in Normal Human Oral Keratinocytes

Li, Xuan; Zha, Junli; Chen, Hongying; Nishitani, Junko; Camargo, Paulo M.; Cole, Steve W.; Zack, Jerome A.

doi:10.1128/jvi.77.6.3470-3476.2003

Cited by 51 publications

(82 citation statements)

References 50 publications

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“…These findings are fully consistent with the results of other studies (70,71,132). However, Liu et al (61) have reported productive infection of oral keratinocytes with X4-and dual-tropic isolates (X4/R5) and minimal infection with R5 isolates. In contrast, Quinones-Mateu et al (91) could not demonstrate infection of oral keratinocytes with either X4 or R5 isolates.…”

Section: Discussionsupporting

confidence: 83%

“…As well, detection of HIV-1 in oral mucosal cells was demonstrated by electron microscopy (91). Recent studies have demonstrated that oral keratinocytes can be infected by HIV-1 using galactosylceramide and CXCR4 as receptors (61), and ethanol may increase infectivity (23). As well, other studies have suggested that HIV-1 infection, both cell free and cell associated, of salivary gland cell lines via CXCR4 and CCR5 with a CD4-independent mechanism can be demonstrated in vitro (70).…”

mentioning

confidence: 99%

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Molecular Interactions of Human Immunodeficiency Virus Type 1 with Primary Human Oral Keratinocytes

Acheampong¹,

Parveen²,

Muthoga³

et al. 2005

J Virol

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Section: Discussionsupporting

confidence: 83%

mentioning

confidence: 99%

Molecular Interactions of Human Immunodeficiency Virus Type 1 with Primary Human Oral Keratinocytes

Acheampong¹,

Parveen²,

Muthoga³

et al. 2005

J Virol

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“…This result is in agreement with that of Quiñones-Mateu et al (42), who found no productive infection in normal oral keratinocytes inoculated with either X4 or R5 viruses. The findings, however, contrast with those of Liu et al (29), who showed infection of oral keratinocytes using high doses of X4 and R5/X4 viruses but not an R5 virus through a CD4-independent mechanism that may involve GalCer and/or CXCR4 as cellular receptors. In another study, Moore et al (35) showed infection of oral keratinocytes with cell-free R5 viruses but not X4 viruses.…”

Section: Discussioncontrasting

confidence: 56%

“…In another study, Moore et al (35) showed infection of oral keratinocytes with cell-free R5 viruses but not X4 viruses. The discrepancies may be due to variations in experimental conditions, such as the use of Polybrene during virus exposure by Liu et al (29) and differences in virus dosages and/or levels of cell surface GalCer, CCR5, and/or CXCR4 expression in the cell models.…”

Section: Discussionmentioning

confidence: 99%

“…Rather, antiviral inhibitors (including SLPI) already present in salivary fluids likely serve this purpose. When initial protective oral defenses are overwhelmed by a bolus of virus (e.g., during breastfeeding, receptive oral sex, and experimentally infected rhesus macaques; reviewed in reference 49), virus can penetrate the mucosa via transcytosis and possibly direct infection (29,35), and create an initial focus of viral replication. Over time, subsequent rounds of replication spread the virus through the tissues and draining lymph nodes, and systemic infection occurs.…”

Section: Discussionmentioning

confidence: 99%

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Human Immunodeficiency Virus Type 1 Stimulates the Expression and Production of Secretory Leukocyte Protease Inhibitor (SLPI) in Oral Epithelial Cells: a Role for SLPI in Innate Mucosal Immunity

Jana¹,

Gray

Shugars

2005

J Virol

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The innate immune response is a key barrier against pathogenic microorganisms such as human immunodeficiency virus type 1 (HIV-1). Because HIV-1 is rarely transmitted orally, we hypothesized that oral epithelial cells participate in the innate immune defense against this virus. We further hypothesized that secretory leukocyte protease inhibitor (SLPI), a 12-kDa mucosal antiviral protein, is a component of the host immune response to this virus. Here we demonstrated constitutive expression and production of SLPI in immortalized human oral keratinocytes. Brief exposure of cells to HIV-1 BaL and HXB2 significantly increased SLPI mRNA and protein production compared to that in mock-exposed cells (P < 0.01), as evaluated by real-time quantitative reverse transcription-PCR and enzyme-linked immunosorbent assay. HIV-1-mediated stimulation of SLPI occurred at the transcriptional level, was dose and time dependent, was elicited by heat-inactivated and infectious viruses, and did not depend on cellular infection. Experiments with purified retroviral proteins showed that the stimulatory effect was induced specifically by external envelope glycoproteins from HIV-1 and simian immunodeficiency virus. SLPI responsiveness to HIV-1 was also observed in an unrelated oral epithelial cell line and in normal (nonimmortalized) human oral epithelial cells isolated from healthy uninfected gingival tissues. In this first report of SLPI regulation by HIV-1, we show that the expression and production of the antimicrobial and anti-inflammatory protein can be stimulated in oral epithelial cells by the virus through interactions with gp120 in the absence of direct infection. These findings indicate that SLPI is a component of the oral mucosal response to HIV-1.

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Detection of human immunodeficiency virus type 1 RNA by in situ hybridization in oral mucosa epithelial cells from anti‐HIV‐1 positive patients

Rodríguez‐Iñigo

Jiménez

Bartolomé

et al. 2005

Journal of Medical Virology

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Several in vitro studies have shown that HIV-1 can infect CD4 negative epithelial cells of different origin including normal human oral keratinocytes, but whether this infection of mucosal epithelial cells occurs in vivo is still unclear. In this report, the presence and cell types infected by HIV-1 in paraffin embedded oral mucosa biopsies from 17 anti-HIV-1 positive patients have been examined by in situ hybridization and immunohistochemistry. As controls, oral mucosa biopsies from eight patients without HIV-1 infection markers were also analyzed. The results showed that 8 out of the 17 anti-HIV-1 positive patients had HIV-1 RNA detectable in plasma. Positive hybridization signals were observed in the mucosa biopsies from 14 of the 17 anti-HIV-1 patients (82.3%). The mean percentage of cells showing HIV-1 RNA was 2.64% +/- 1.77% (range: 1% to 5.5%). No differences in the mean percentage of HIV-1 infected cells were found between patients with and without HIV-1 RNA in plasma (3.01% +/- 1.57% vs. 3.4% +/- 1.27% respectively), or between untreated patients and patients under antiretroviral therapy (2.83% +/- 1.63% vs. 3.42% +/- 1.29% respectively). Immunohistochemical detection of S-100 antigen, cytokeratin and CD4 showed that hybridization signals appeared in cytokeratin positive cells and CD4 positive cells but not in S-100 positive cells. In conclusion, this study has demonstrated that HIV-1 infects and replicates in oral mucosa epithelial cells in vivo and that these cells could represent a reservoir of the virus that may escape to the currently used antiretroviral therapy.

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Human Immunodeficiency Virus Type 1 Infection and Replication in Normal Human Oral Keratinocytes

Cited by 51 publications

References 50 publications

Molecular Interactions of Human Immunodeficiency Virus Type 1 with Primary Human Oral Keratinocytes

Molecular Interactions of Human Immunodeficiency Virus Type 1 with Primary Human Oral Keratinocytes

Human Immunodeficiency Virus Type 1 Stimulates the Expression and Production of Secretory Leukocyte Protease Inhibitor (SLPI) in Oral Epithelial Cells: a Role for SLPI in Innate Mucosal Immunity

Detection of human immunodeficiency virus type 1 RNA by in situ hybridization in oral mucosa epithelial cells from anti‐HIV‐1 positive patients

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