Alcohol Enhances HIV Type 1 Infection in Normal Human Oral Keratinocytes by Up-regulating Cell-Surface CXCR4 Coreceptor

Abstract

Recent studies suggest that normal human oral keratinocytes (NHOKs) can be infected by HIV-1, and alcohol can enhance HIV infection and replication in lymphocytes. In this study, we examined the possibility that alcohol might facilitate HIV-1 infection of NHOKs by up-regulating cell surface expression of the coreceptor, CXCR4. Alcohol enhanced in vitro infection of NHOKs by CXCR4-tropic strains of HIV-1 as indicated by synthesis of viral reverse transcripts and production of p24gag protein. Alcohol had no effect on CXCR4 gene expression or on total cellular complements of CXCR4 protein. However, alcohol did enhance the fraction of total CXCR4 expressed on the cell surface relative to intracellular stores. Alcohol-induced up-regulation of cell surface CXCR4 expression and HIV-1 infectivity could be blocked by SDF-1alpha-mediated internalization. These data suggest that alcohol may influence oral HIV transmission by altering the cellular compartmentalization of CXCR4 in cells of the oral cavity.

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

“…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).…”

Effects of Highly Active Antiretroviral Therapy on HIV-1-Associated Oral Complications

“…Data from our laboratory suggests the presence of polyamines usually found in higher concentrations in semen could enhance HIV-1 infection of primary human oral keratinocytes [1]. Similarly, other cofactors such as alcohol enhances HIV-1 infectivity of primary oral epithelial culture by enhancing the expression of CXCR4 [24]. The issue of HIV-1 infection and oral epithelial chemokines receptors have been briefly described [87], however, more elaborate studies are required to dissect the mechanisms involved with HIV pathogenesis in oral mucosa in conjunction with other co-factors.…”

“…This situation is alarming and necessitates complete understanding of the effects of HAART on the oral cavity due to its major influence on the quality of life for the HIV infected population. Although the transmission of viral infection through the oral cavity has always been questioned, several studies have shown that the oral epithelial cells can be infected both in vitro [1,24,87,104] and in vivo [123]. The results of these studies, coupled with numerous reports suggesting mother-to-child transmission [113,136] have necessitated the institution of studies aimed at understanding HIV pathogenesis in the oral cavity.…”

Drugs of abuse and HIV infection/replication: Implications for mother–fetus transmission

“…Liu et al showed that alcohol enhanced the entry of CXCR4-tropic HIV into peripheral blood lymphocytes (PBLs) ten-fold compared to untreated cells (Liu et al 2003). Alcohol enhances HIV infection of normal human oral keratinocytes by up-regulating CXCR4 expression (Chen et al 2004). These in vitro findings are validated in the animal studies.…”