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

Acheampong, Edward; Parveen, Zahida; Muthoga, Lois W.; Wasmuth-Peroud, Vivian; Kalayeh, Mehrnush; Bashir, Adnan; Diecidue, Robert J.; Mukhtār, Muḥammad; Pomerantz, Roger J.

doi:10.1128/jvi.79.13.8440-8453.2005

Cited by 23 publications

(24 citation statements)

References 125 publications

(114 reference statements)

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“…MLVpp and VSVpp infected Caco-2 cells less efficiently when the cells were polarized, suggesting that the expression of both MLV and VSV receptors is modulated upon cell polarization or that NL4.3 promoter activity is suboptimal in polarized cells. Our experiments suggest that the HIV promoter long terminal repeat is reduced in polarized Caco-2 cells (data not shown), consistent with a report from Acheampong and colleagues (1). Normalization of HCVpp infection of polarized and nonpolarized Caco-2 cells relative to MLVpp or VSVpp demonstrated a nonsignificant two-to threefold increase in HCV gp-dependent entry in polarized Caco-2 cells.…”

Section: Effect(s) Of Cell Polarization On Hcv Receptor Expressionsupporting

confidence: 92%

Effect of Cell Polarization on Hepatitis C Virus Entry

Mee

Grove

Harris

et al. 2008

J Virol

104

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The primary reservoir for hepatitis C virus (HCV) replication in vivo is believed to be hepatocytes within the liver. Three host cell molecules have been reported to be important entry factors for receptors for HCV: the tetraspanin CD81, scavenger receptor BI (SR-BI), and the tight-junction (TJ) protein claudin 1 (CLDN1). The recent discovery of a TJ protein as a critical coreceptor highlighted the importance of studying the effect(s) of TJ formation and cell polarization on HCV entry. The colorectal adenocarcinoma Caco-2 cell line forms polarized monolayers containing functional TJs and was found to express the CD81, SR-BI, and CLDN1 proteins. Viral receptor expression levels increased upon polarization, and CLDN1 relocalized from the apical pole of the lateral cell membrane to the lateral cell-cell junction and basolateral domains. In contrast, expression and localization of the TJ proteins ZO-1 and occludin 1 were unchanged upon polarization. HCV infected polarized and nonpolarized Caco-2 cells to comparable levels, and entry was neutralized by anti-E2 monoclonal antibodies, demonstrating glycoprotein-dependent entry. HCV pseudoparticle infection and recombinant HCV E1E2 glycoprotein interaction with polarized Caco-2 cells occurred predominantly at the apical surface. Disruption of TJs significantly increased HCV entry. These data support a model where TJs provide a physical barrier for viral access to receptors expressed on lateral and basolateral cellular domains.Hepatitis C virus (HCV) is an enveloped positive-stranded RNA virus and the sole member of the Hepacivirus genus, within the family Flaviviridae. Worldwide, approximately 170 million individuals are infected with HCV and a significant fraction of these people are at risk of developing serious progressive liver disease. The principal reservoir for viral replication is believed to be hepatocytes within the liver. The recent development of the retrovirus pseudoparticle system (HCVpp) (5, 25) and the ability of the JFH-1 strain of HCV to release infectious particles in cell culture (HCVcc) (30,45,51) have allowed studies on the mechanism of HCV entry and replication.Viruses initiate infection by attaching to molecules or receptors on the cell surface. Expression and localization of these receptors are often important determinants of a cell's susceptibility to infection and of virus tropism for particular tissues. The observation that HCVpp only infect human liver-derived cell lines in vitro suggests that liver-specific receptors contribute to defining the hepatotropism of HCV. Current evidence suggests that at least three host cell molecules are important for HCV entry in vitro, i.e., the tetraspanin CD81 (5, 25, 35), scavenger receptor class B member I (SR-BI) (5,23,26,39), and tight-junction (TJ) protein claudin 1 (CLDN1) (19). Recent data suggest that CLDN6 and CLDN9 can also function as coreceptors allowing HCV entry (33, 50). HCV glycoproteins (gps) have been reported to interact directly with CD81 and SR-BI (reviewed in reference 11). Mutagenesis...

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Section: Effect(s) Of Cell Polarization On Hcv Receptor Expressionsupporting

confidence: 92%

Effect of Cell Polarization on Hepatitis C Virus Entry

Mee

Grove

Harris

et al. 2008

J Virol

104

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“…In their extracellular forms, Tat and gp120 target different non-HIV-infected/HIV-nonpermissive cells, contributing to the development of several AIDS-associated pathologies. In particular, Tat and gp120 cooperate in inducing oxidative stress in blood-brain barrier endothelial cells (ECs) (38) and apoptosis in cardiomyocytes (18), neurons (53), and keratinocytes (1). Taken together, these observations provide the opportunity to develop multitargeted therapies aimed at blocking gp120 and Tat simultaneously.…”

mentioning

confidence: 99%

Heparin-Mimicking Sulfonic Acid Polymers as Multitarget Inhibitors of Human Immunodeficiency Virus Type 1 Tat and gp120 Proteins

Bugatti

Urbinati

Ravelli

et al. 2007

Antimicrob Agents Chemother

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Human immunodeficiency virus (HIV) Tat and gp120 intriguingly share the feature of being basic peptides that, once released by HIV ؉ cells, bind to polyanionic heparan sulfate proteoglycans (HSPGs) on target uninfected cells, contributing to the onset of AIDS-associated pathologies. To identify multitarget anti-HIV prodrugs, we investigated the gp120 and Tat antagonist potentials of a series of polyanionic synthetic sulfonic acid polymers (SSAPs). Surface plasmon resonance revealed that SSAPs inhibit with a competitive mechanism of action the binding of Tat and gp120 to surface-immobilized heparin, an experimental condition that resembles binding to cellular HSPGs. Accordingly, SSAPs inhibited HSPG-dependent cell internalization and the transactivating activity of Tat. Little is known about the binding of free gp120 to target cells. Here, we identified two classes of gp120 receptors expressed on endothelial cells, one of which was consistent with an HSPG-binding, low-affinity/high-capacity receptor that is inhibited by free heparin. SSAPs inhibited the binding of free gp120 to endothelial cells, as well as its capacity to induce apoptosis in the same cells. In all the assays, poly(4-styrenesulfonic acid) (PSS) proved to be the most potent antagonist of Tat and gp120. Accordingly, PSS bound both proteins with high affinity. In conclusion, SSAPs represent an interesting class of compounds that bind both gp120 and Tat and inhibit their HSPG-dependent cell surface binding and pathological effects. As these activities contribute to both AIDS progression and associated pathologies, SSAPs can be considered prototypic molecules for the development of multitarget drugs for the treatment of HIV infection and AIDS-associated pathologies.

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“…Interaction of these fluids could have a potential for enhancing the infectivity of oral epithelium. 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].…”

Section: Dmentioning

confidence: 98%

“…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.…”

Section: Introductionmentioning

confidence: 97%

“…This is followed by other oral ailments such as hairy leukoplakia (19.7%), gingival/periodontal lesions (2.9%) and Kaposi Sarcoma (1.5%) [6]. Particularly infection of the oral mucosa [1] and an increase in the incidence of oral lesions such as oral warts in the era of HAART [48] and the inability of this aggressive antiviral therapeutic regimen to control oral lesions among children [45,178] warrants studies aimed at understanding the clinical implications of various antiretrovirals on the oral epithelium.…”

Section: Introductionmentioning

confidence: 98%

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

Parveen¹,

Acheampong²,

Pomerantz³

et al. 2007

CHR

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The oral cavity of human immunodeficiency virus type I (HIV-1) infected individuals is subjected to a series of opportunistic infections which are usually considered as a prognostic marker for the severity of infection as well as an indicator of immunodeficiency. The highly active antiretroviral therapy (HAART) has significantly lessened the severity of HIV-associated oral infections although this therapeutic regimen is considered to be responsible for some of the oral lesions such as oral warts and salivary gland disorders. In addition, the beneficial effects of HAART on HIV associated oral lesions are stratified with age, with the adult population showing improvements whereas the oral lesions among children remain unchanged with this therapy. The presence of HIV-1 in the saliva, and infectivity of oral epithelial cells suggest that the oral cavity is a site of HIV pathogenesis and potential reservoir for the disease in the setting of virally suppressive HAART. Overall HIV associated oral lesions are usually due to fungal, bacterial, and viral infections as well as some of unknown etiology. This review describes the current status of HIV associated oral lesions by comparing historically available pre-HAART data. Future directions envisioned by the National Institutes of Health as well as novel avenues to be explored are also presented.

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

Cited by 23 publications

References 125 publications

Effect of Cell Polarization on Hepatitis C Virus Entry

Effect of Cell Polarization on Hepatitis C Virus Entry

Heparin-Mimicking Sulfonic Acid Polymers as Multitarget Inhibitors of Human Immunodeficiency Virus Type 1 Tat and gp120 Proteins

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

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