Herpes simplex virus type 1 infection of polarized epithelial cells requires microtubules and access to receptors present at cell–cell contact sites

Marozin, Sabrina; Prank, Ute; Sodeik, Beate

doi:10.1099/vir.0.19530-0

Cited by 43 publications

(41 citation statements)

References 46 publications

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“…Previous studies have reported on HSV infection of epithelial cells by either the basolateral surface (25,38) or by both the apical and basolateral surfaces (16,17,25,39,46,47,55). HSV can apparently enter HaCaT keratinocytes from either the apical or the basolateral surfaces by endocytosis, although the basolateral domain seems to be preferred at low MOI ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…6A). The preference of HSV for infecting exterior cells of Madin-Darby canine kidney cell islets has been noted previously (25,38). At high MOI, however, HSV entered (Fig.…”

Section: Lysosomotropic Agents Inhibit Hsv Infection Of Human Keratinmentioning

confidence: 95%

“…5 and 6). HSV infection of Madin-Darby canine kidney (MDCK) cells is facilitated by disruption of cell junctions, either by mechanical wounding (17,38) or by calcium depletion (17,25,46,55), suggesting that HSV also favors the basolateral surfaces of MDCK cells.…”

Section: Discussionmentioning

confidence: 99%

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Herpes Simplex Virus Type 1 Enters Human Epidermal Keratinocytes, but Not Neurons, via a pH-Dependent Endocytic Pathway

Nicola

Hou

Major

et al. 2005

J Virol

220

242

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Herpes simplex virus (HSV) enters some laboratory cell lines via a pH-dependent, endocytic mechanism. We investigated whether this entry pathway is used in human cell types relevant to pathogenesis. Three different classes of lysosomotropic agents, which raise endosomal pH, blocked HSV entry into primary and transformed human keratinocytes, but not into human neurons or neuroblastoma lines. In keratinocytes, incoming HSV particles colocalized with markers of endocytic uptake. Treatment with the isoflavone genistein, an inhibitor of protein tyrosine kinases, reduced the delivery of incoming viral particles to the nuclear periphery and virusinduced gene expression in keratinocytes but not neurons. Moreover, in keratinocyte monolayer islets, HSV infected both the inner and outer cells in a genistein-sensitive manner, suggesting viral endocytosis from both basolateral and apical plasma membrane surfaces. Together, the results indicate that HSV enters human epidermal keratinocytes, but not neurons, by a low-pH, endocytic pathway that is dependent on host tyrosine phosphorylation. Thus, HSV utilizes fundamentally different cellular entry pathways to infect important target cell populations.

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Section: Discussionmentioning

confidence: 99%

“…6A). The preference of HSV for infecting exterior cells of Madin-Darby canine kidney cell islets has been noted previously (25,38). At high MOI, however, HSV entered (Fig.…”

Section: Lysosomotropic Agents Inhibit Hsv Infection Of Human Keratinmentioning

confidence: 95%

See 1 more Smart Citation

Herpes Simplex Virus Type 1 Enters Human Epidermal Keratinocytes, but Not Neurons, via a pH-Dependent Endocytic Pathway

Nicola

Hou

Major

et al. 2005

J Virol

220

242

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“…Accordingly, actin and microtubules are required for the efficient entry of herpes simplex type 1 and simian virus 40, respectively (Pelkmans et al, 2002;Marozin et al, 2004). It has been shown that disrupting the actin network can inhibit infection of HIV-1 and fusion with the host cell (Iyengar et al, 1998;Jernigan et al, 2000), presumably by disrupting the colocalization of CD4 and CXCR4 (Iyengar et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Histone Deacetylase 6 Regulates Human Immunodeficiency Virus Type 1 Infection

Valenzuela-Fernández

Álvarez

Gordon-Alonso

et al. 2005

MBoC

115

212

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Efficient human immunodeficiency virus (HIV)-1 infection depends on multiple interactions between the viral gp41/gp120envelope (Env) proteins and cell surface receptors. However, cytoskeleton-associated proteins that modify membrane dynamics may also regulate the formation of the HIV-mediated fusion pore and hence viral infection. Because the effects of HDAC6-tubulin deacetylase on cortical ␣-tubulin regulate cell migration and immune synapse organization, we explored the possible role of HDAC6 in HIV-1-envelope-mediated cell fusion and infection. The binding of the gp120 protein to CD4؉ -permissive cells increased the level of acetylated ␣-tubulin in a CD4-dependent manner. Furthermore, overexpression of active HDAC6 inhibited the acetylation of ␣-tubulin, and remarkably, prevented HIV-1 envelopedependent cell fusion and infection without affecting the expression and codistribution of HIV-1 receptors. In contrast, knockdown of HDAC6 expression or inhibition of its tubulin deacetylase activity strongly enhanced HIV-1 infection and syncytia formation. These results demonstrate that HDAC6 plays a significant role in regulating HIV-1 infection and Env-mediated syncytia formation. INTRODUCTIONHuman immunodeficiency virus (HIV) infection is initiated by the virus binding to the cell surface after CD4 engagement and HIV-1 fusion with the plasma membrane (Stein et al., 1987;Maddon et al., 1988;McClure et al., 1988;Moore et al., 1997). The main coreceptors for HIV-1 infection have been shown to be CXCR4 and CCR5, which represented a major advance in understanding the mechanism of the HIV-1 infection (Cocchi et al., 1995;Alkhatib et al., 1996;Bleul et al., 1996;Choe et al., 1996;Deng et al., 1996;Doranz et al., 1996;Dragic et al., 1996;Feng et al., 1996). As a result, it has been proposed that the sequential binding of gp120 viral protein to CD4 and to one coreceptor induces specific conformational changes in gp41, facilitating viral fusion with cell membrane (Clapham and McKnight, 2002).The cell cytoskeleton is involved in the early events of viral infection, regulating viral penetration and genome uncoating, the movement of viral capsids, and integration of the viral genome. Accordingly, actin and microtubules are required for the efficient entry of herpes simplex type 1 and simian virus 40, respectively (Pelkmans et al., 2002;Marozin et al., 2004). It has been shown that disrupting the actin network can inhibit infection of HIV-1 and fusion with the host cell (Iyengar et al., 1998;Jernigan et al., 2000), presumably by disrupting the colocalization of CD4 and CXCR4 (Iyengar et al., 1998). In addition, the actin cytoskeleton seems to be necessary for activation of the reverse transcription complex (Bukrinskaya et al., 1998). However, little is known about the role of cytoskeleton-related enzymes in the control of HIV fusion and infection.Histone deacetylase 6 (HDAC6) is exclusively located in the cytoplasm, and it regulates the acetylation of ␣-tubulin (Hubbert et al., 2002;Matsuyama et al., 2002;Haggarty et al., 2003;Z...

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“…This process is aided by viral capsid protein VP26 and tegument protein U L 34. The capsids are propelled through the negative end of microtubules and released into nucleus through nuclear pore complexes (NPCs) [46][47][48][49][50].…”

Section: Viral Entrymentioning

confidence: 99%

Update On Emerging Antivirals For The Management Of Herpes Simplex Virus Infections: A Patenting Perspective

Vadlapudi¹,

Vadlapatla²,

Mitra³

2013

Recent Patents on Anti-Infective Drug Discovery

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Herpes simplex virus (HSV) infections can be treated efficiently by the application of antiviral drugs. The herpes family of viruses is responsible for causing a wide variety of diseases in humans. The standard therapy for the management of such infections includes acyclovir (ACV) and penciclovir (PCV) with their respective prodrugs valaciclovir and famciclovir. Though effective, long term prophylaxis with the current drugs leads to development of drug-resistant viral isolates, particularly in immunocompromised patients. Moreover, some drugs are associated with dose-limiting toxicities which limit their further utility. Therefore, there is a need to develop new antiherpetic compounds with different mechanisms of action which will be safe and effective against emerging drug resistant viral isolates. Significant advances have been made towards the design and development of novel antiviral therapeutics during the last decade. As evident by their excellent antiviral activities, pharmaceutical companies are moving forward with several new compounds into various phases of clinical trials. This review provides an overview of structure and life cycle of HSV, progress in the development of new therapies, update on the advances in emerging therapeutics under clinical development and related recent patents for the treatment of Herpes simplex virus infections.

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Herpes simplex virus type 1 infection of polarized epithelial cells requires microtubules and access to receptors present at cell–cell contact sites

Cited by 43 publications

References 46 publications

Herpes Simplex Virus Type 1 Enters Human Epidermal Keratinocytes, but Not Neurons, via a pH-Dependent Endocytic Pathway

Herpes Simplex Virus Type 1 Enters Human Epidermal Keratinocytes, but Not Neurons, via a pH-Dependent Endocytic Pathway

Histone Deacetylase 6 Regulates Human Immunodeficiency Virus Type 1 Infection

Update On Emerging Antivirals For The Management Of Herpes Simplex Virus Infections: A Patenting Perspective

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