MATHEMATICAL STUDY OF IN-HOST DYNAMICS OF HERPES SIMPLEX VIRUS TYPE 2 TO ASSESS THE IMPACT OF IMMUNE RESPONSE

2017 ◽  
Vol 25 (01) ◽  
pp. 47-70
Author(s):  
CHANDRA N. PODDER ◽  
SYEDA ELHAM SHAHED ◽  
OLUWASEUN SHAROMI ◽  
SAMIR K. BHOWMIK
Keyword(s):  
Immune Response ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Deterministic Model ◽  
Humoral Immune ◽  
Cell Mediated Immune Response ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2 ◽  
The Impact

A new deterministic model for Herpes Simplex Virus-2 (HSV-2) in vivo, which incorporates the cell-mediated and humoral immune responses, is designed and analyzed. The analyses of the model reveal that it has a globally-asymptotically stable (GAS) virus-free equilibrium (VFE) whenever the associated reproduction threshold is less than unity. Also, it has at least one virus-present equilibrium (VPE) when the reproduction threshold exceeds unity (and virus will persist in vivo under this condition). Furthermore, it is shown that a Herpes Simplex Virus-2 (HSV-2) vaccine will be effective in reducing HSV-2 burden in vivo if it reduces the ability of the virus without glycoprotein C (gC) to bind to the host cell or if it reduces the re-activation rate of latent HSV-2. Additionally, the vaccine will also be very effective if it results in an increase in the fraction of the re-activated latent viruses without gC. Numerical simulations of the model show that cell-mediated immune response is more effective (in controlling HSV-2 burden in vivo) than humoral immune response (the latter only offers marginal impact in reducing HSV-2 burden in vivo, except if its effectiveness level is very high). Thus, a future HSV-2 vaccine that boosts cell-mediated immune response is expected to be quite effective in controlling HSV-2 in vivo.

The effect of the antiherpesvirus drug 5-methoxymethyl-2′-deoxyuridine on the humoral immune response in vivo

1977 ◽  
Vol 23 (8) ◽  
pp. 1059-1061 ◽  
Author(s):  
Barry T. Rouse ◽  
Lorne A. Babiuk ◽  
V. Sagar Gupta
Keyword(s):  
Immune Response ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Immune Responses ◽  
Humoral Immune Response ◽  
Humoral Immune ◽  
Simplex Virus

5-Methoxymethyl-2′-deoxyuridine (MMUdR), a drug with potent antiviral activity in vitro against Herpes simplex virus, was investigated for its immunosuppressive effects. Doses as high as 2000 mg/kg given daily for 9 days were not immunosuppressive as judged by the fact that treated animals produced normal immune responses to sheep erythrocytes, Brucella bacteria, and Herpes simplex virus.

scholarly journals T Cell-Derived Lymphotoxin Is Essential for the Anti-Herpes Simplex Virus 1 Humoral Immune Response

2018 ◽  
Vol 92 (14) ◽  
Author(s):  
Kaiting Yang ◽  
Yong Liang ◽  
Zhichen Sun ◽  
Diyuan Xue ◽  
Hairong Xu ◽  
...  
Keyword(s):  
Immune Response ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Humoral Immune Response ◽  
Herpes Simplex Virus 1 ◽  
Humoral Immune ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTB cell-derived lymphotoxin (LT) is required for the development of follicular dendritic cell clusters for the formation of primary and secondary lymphoid follicles, but the role of T cell-derived LT in antibody response has not been well demonstrated. We observed that lymphotoxin β-receptor (LTβR) signaling is essential for optimal humoral immune response and protection against an acute herpes simplex virus 1 (HSV-1) infection. Blocking the LTβR pathway caused poor maintenance of germinal center B (GC-B) cells and follicular helper T (Tfh) cells. Using bone marrow chimeric mice and adoptive transplantation, we determined that T cell-derived LT played an indispensable role in the humoral immune response to HSV-1. Upregulation of gamma interferon by the LTβR-Ig blockade impairs the sustainability of Tfh-like cells, leading to an impaired humoral immune response. Our findings have identified a novel role of T cell-derived LT in the humoral immune response against HSV-1 infection.IMPORTANCEImmunocompromised people are susceptible to HSV-1 infection and lethal recurrence, which could be inhibited by anti-HSV-1 humoral immune response in the host. This study sought to explore the role of T cell-derived LT in the anti-HSV-1 humoral immune response using LT-LTβR signaling-deficient mice and the LTβR-Ig blockade. The data indicate that the T cell-derived LT may play an essential role in sustaining Tfh-like cells and ensure Tfh-like cells' migration into primary or secondary follicles for further maturation. This study provides insights for vaccine development against infectious diseases.

scholarly journals Entry Mechanisms of Herpes Simplex Virus 1 into Murine Epidermis: Involvement of Nectin-1 and Herpesvirus Entry Mediator as Cellular Receptors

2014 ◽  
Vol 89 (1) ◽  
pp. 262-274 ◽  
Author(s):  
Philipp Petermann ◽  
Katharina Thier ◽  
Elena Rahn ◽  
Frazer J. Rixon ◽  
Wilhelm Bloch ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Ex Vivo ◽  
Target Tissue ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus ◽  
The Impact ◽  
Herpesvirus Entry Mediator ◽  
Hsv 1

ABSTRACTSkin keratinocytes represent a primary entry site for herpes simplex virus 1 (HSV-1)in vivo. The cellular proteins nectin-1 and herpesvirus entry mediator (HVEM) act as efficient receptors for both serotypes of HSV and are sufficient for disease development mediated by HSV-2 in mice. How HSV-1 enters skin and whether both nectin-1 and HVEM are involved are not known. We addressed the impact of nectin-1 during entry of HSV-1 into murine epidermis and investigated the putative contribution of HVEM. Usingex vivoinfection of murine epidermis, we showed that HSV-1 entered the basal keratinocytes of the epidermis very efficiently. In nectin-1-deficient epidermis, entry was strongly reduced. Almost no entry was observed, however, in nectin-1-deficient keratinocytes grown in culture. This observation correlated with the presence of HVEM on the keratinocyte surface in epidermis and with the lack of HVEM expression in nectin-1-deficient primary keratinocytes. Our results suggest that nectin-1 is the primary receptor in epidermis, while HVEM has a more limited role. For primary murine keratinocytes, on which nectin-1 acts as a single receptor, electron microscopy suggested that HSV-1 can enter both by direct fusion with the plasma membrane and via endocytic vesicles. Thus, we concluded that nectin-1 directs internalization into keratinocytes via alternative pathways. In summary, HSV-1 entry into epidermis was shown to strongly depend on the presence of nectin-1, but the restricted presence of HVEM can potentially replace nectin-1 as a receptor, illustrating the flexibility employed by HSV-1 to efficiently invade tissuein vivo.IMPORTANCEHerpes simplex virus (HSV) can cause a range of diseases in humans, from uncomplicated mucocutaneous lesions to life-threatening infections. The skin is one target tissue of HSV, and the question of how the virus overcomes the protective skin barrier and penetrates into the tissue to reach its receptors is still open. Previous studies analyzing entry into cells grownin vitrorevealed nectin-1 and HVEM as HSV receptors. To explore the contributions of nectin-1 and HVEM to entry into a natural target tissue, we established anex vivoinfection model. Using nectin-1- or HVEM-deficient mice, we demonstrated the distinct involvement of nectin-1 and HVEM for HSV-1 entry into epidermis and characterized the internalization pathways. Such advances in understanding the involvement of receptors in tissue are essential preconditions for unraveling HSV invasion of skin, which in turn will allow the development of antiviral reagents.

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