Mucosal Herpes Immunity and Immunopathology to Ocular and Genital Herpes Simplex Virus Infections

Chentoufi, Aziz Alami; BenMohamed, Lbachir

doi:10.1155/2012/149135

Cited by 38 publications

(61 citation statements)

References 232 publications

(350 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To determine whether the interaction of galectin-3 was specific to HSV-1, we performed additional pulldown assays with HSV-2, a distinct but closely related virus traditionally associated with genital disease (29,30). Interestingly, the two replication-defective HSV-2 mutant virus strains used in this study, dl5 and dl29, did not bind to galectin-3 beads in affinity columns (Fig.…”

Section: Hsv-1 Binds To Human Galectin-3mentioning

confidence: 95%

Binding of Transmembrane Mucins to Galectin-3 Limits Herpesvirus 1 Infection of Human Corneal Keratinocytes

Woodward

Mauris

Argüeso

2013

J Virol

View full text Add to dashboard Cite

Epithelial cells lining mucosal surfaces impose multiple barriers to viral infection. At the ocular surface, the carbohydrate-binding protein galectin-3 maintains barrier function by cross-linking transmembrane mucins on the apical glycocalyx. Despite these defense mechanisms, many viruses have evolved to exploit fundamental cellular processes on host cells. Here, we use affinity assays to show that herpes simplex virus type 1 (HSV-1), but not HSV-2, binds human galectin-3. Knockdown of galectin-3 in human corneal keratinocytes by small interfering RNA significantly impaired HSV-1 infection, but not expression of nectin-1, indicating that galectin-3 is a herpesvirus entry mediator. Interestingly, exposure of epithelial cell cultures to transmembrane mucin isolates decreased viral infectivity. Moreover, HSV-1 failed to elute the biological counterreceptor MUC16 from galectin-3 affinity columns, suggesting that association of transmembrane mucins to galectin-3 provides protection against viral infection. Together, these results indicate that HSV-1 exploits galectin-3 to enhance virus attachment to host cells and support a protective role for transmembrane mucins under physiological conditions by masking viral entry mediators on the epithelial glycocalyx.

show abstract

Section: Hsv-1 Binds To Human Galectin-3mentioning

confidence: 95%

Binding of Transmembrane Mucins to Galectin-3 Limits Herpesvirus 1 Infection of Human Corneal Keratinocytes

Woodward

Mauris

Argüeso

2013

J Virol

View full text Add to dashboard Cite

show abstract

“…However, there are two concerns regarding mouse models compared to other models: ( i ) HSV-1 spontaneous reactivation is either extremely rare or does not occur in mice [38] in contrast to rabbits where spontaneous reactivation occurs at levels similar to that of humans; and ( ii ) although induction of a systemic immune response (e.g. neutralizing antibody) or a passive transfer of CD8 + T cells can protect the mouse, it does protect humans against ocular herpes disease [2–4, 37, 39, 86]. Such differences make herpes vaccine candidates, developed based on mouse pre-clinical studies, difficult to extrapolate to humans.…”

Section: Discussionmentioning

confidence: 99%

The challenges and opportunities for the development of a T-cell epitope-based herpes simplex vaccine

Kuo

Wang

Badakhshan

et al. 2014

Vaccine

Self Cite

View full text Add to dashboard Cite

The infections with herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) have been prevalent since the ancient Greek times. To this day, they still affect a staggering number of over a half billion individuals worldwide. HSV-2 infections cause painful genital herpes, encephalitis, and death in newborns. HSV-1 infections are more prevalent than HSV-2 infections and cause potentially blinding ocular herpes, oro-facial herpes and encephalitis. While genital herpes in mainly caused by HSV-2 infections, in recent years, there is an increase in the proportion of genital herpes caused by HSV-1 infections in young adults, which reach 50% in some western societies. While prophylactic and therapeutic HSV vaccines remain urgently needed for centuries their development has been notoriously difficult. During the most recent National Institute of Health (NIH) workshop titled "Next Generation Herpes Simplex Virus Vaccines: The Challenges and Opportunities", basic researchers, funding agencies, and pharmaceutical representatives gathered: (i) to assess the status of herpes vaccine research; and (ii) to identify the gaps and propose alternative approaches in developing a safe and efficient herpes vaccine. One “common denominator” among previously failed clinical herpes vaccine trials is that they either used a whole virus or whole viral proteins, which contain both pathogenic “symptomatic” and protective “asymptomatic” antigens/epitopes. In this report, we continue to advocate that using an “asymptomatic” epitope-based vaccine strategy that selectively incorporates protective epitopes which: (i) are exclusively recognized, in vitro, by effector memory CD4+ and CD8+ TEM cells from “naturally” protected seropositive asymptomatic individuals; and (ii) protect, in vivo, human leukocyte antigen (HLA) transgenic animal models from ocular and genital herpes infections and diseases, could be the answer to many of the scientific challenges facing HSV vaccine development. We review the role of animal models in herpes vaccine development and discuss its current status, challenges, and prospects.

show abstract

“…88,89 Importantly, Tregs serve an indispensable function in orchestrating these effector responses. Upon intravaginal challenge of mice with HSV-2, CD11b+ submucosal DCs and plasmacytoid DCs provide early antigen presentation, 90 and IFN, 91 respectively.…”

Section: Chronic Infectionsmentioning

confidence: 99%

The Immune Fulcrum

Richert-Spuhler

Lund

2015

Progress in Molecular Biology and Translational Science

View full text Add to dashboard Cite

Regulatory T cells (Tregs) are indispensable for immune homeostasis and the prevention of autoimmunity. In the context of infectious diseases, Tregs are multidimensional. Here, we describe how they may potentiate effector responses by assisting in recruitment of T cells into the infection site to resolve infection, facilitate accelerated antigen-specific memory responses, limit pathology, and contribute to disease resolution and healing, to the great benefit of the host. We also explore the villainous functions of Tregs during infection by reviewing several diseases in which the depletion or reduction in Treg frequency allows for better generation of effector memory, and results in acute resolution of infection, as opposed to chronicity or severe long-term outcomes. We describe findings generated using mouse models of infection as well as experiments performed using human cells and tissues. We propose that Tregs represent an immunologic fulcrum, promoting both pathogen clearance and damage control by preventing excessive destruction of infected tissues though unchecked immune responses.

show abstract

Mucosal Herpes Immunity and Immunopathology to Ocular and Genital Herpes Simplex Virus Infections

Cited by 38 publications

References 232 publications

Binding of Transmembrane Mucins to Galectin-3 Limits Herpesvirus 1 Infection of Human Corneal Keratinocytes

Binding of Transmembrane Mucins to Galectin-3 Limits Herpesvirus 1 Infection of Human Corneal Keratinocytes

The challenges and opportunities for the development of a T-cell epitope-based herpes simplex vaccine

The Immune Fulcrum

Contact Info

Product

Resources

About