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

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.

2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Jue Hou ◽  
Zili Zhang ◽  
Qiang Huang ◽  
Jun Yan ◽  
Xiaohu Zhang ◽  
...  

2002 ◽  
Vol 46 (6) ◽  
pp. 1766-1772 ◽  
Author(s):  
Ulrich A. K. Betz ◽  
Rüdiger Fischer ◽  
Gerald Kleymann ◽  
Martin Hendrix ◽  
Helga Rübsamen-Waigmann

ABSTRACT BAY 57-1293 belongs to a new class of antiviral compounds and inhibits replication of herpes simplex virus (HSV) type 1 and type 2 in the nanomolar range in vitro by abrogating the enzymatic activity of the viral primase-helicase complex. In various rodent models of HSV infection the antiviral activity of BAY 57-1293 in vivo was found to be superior compared to all compounds currently used to treat HSV infections. The compound shows profound antiviral activity in murine and rat lethal challenge models of disseminated herpes, in a murine zosteriform spread model of cutaneous disease, and in a murine ocular herpes model. It is active in parenteral, oral, and topical formulations. BAY 57-1293 continued to demonstrate efficacy when the onset of treatment was initiated after symptoms of herpetic disease were already apparent.


2000 ◽  
Vol 44 (9) ◽  
pp. 2471-2474 ◽  
Author(s):  
N. Bourne ◽  
L. R. Stanberry ◽  
E. R. Kern ◽  
G. Holan ◽  
B. Matthews ◽  
...  

ABSTRACT Dendrimers are large highly branched macromolecules synthesized from a polyfunctional core. They have shown a variety of biological properties, including, in some instances, antiviral activity. In this study, five dendrimers were evaluated for in vitro activity against herpes simplex virus (HSV) types 1 and 2 by cytopathic effect (CPE) inhibition and plaque reduction (PR) assay in human foreskin fibroblast cells. All of the compounds were active against both virus types in the CPE inhibition assay, in which drug was added to the cells prior to the addition of virus. Antiviral activity was reduced or lost in the PR assays, in which the cells were incubated with the virus before the drug was added. The prophylactic efficacy suggested that the dendrimers might have potential as topical microbicides, products intended to be applied to the vaginal or rectal mucosa to protect against sexually transmitted infections. Three dendrimers were evaluated for this application against genital HSV infection in mice. Two of the compounds, BRI-2999 and BRI-6741, significantly reduced infection rates when 15 μl of a 100-mg/ml solution was administered immediately prior to intravaginal challenge, and the most effective compound, BRI-2999, provided significant protection even when applied 30 min before challenge. This is the first report of microbicidal activity by dendrimers in vivo.


Author(s):  
Gislaine Franco de Moura- Costa ◽  
Gean Pier Panizzon ◽  
Thalita Zago Oliveira ◽  
Marco Antonio Costa ◽  
João Carlos Palazzo de Mello ◽  
...  

Herpes simplex virus (HSV) type 1 and type 2 are responsible for causing infections whose symptoms can vary from subclinical to severe manifestations. Cordia americana is a plant used by traditional communities for the treatment of wounds and diarrhoea, as well as infections like flu and syphilis. Scientific evidence has shown that, among other biological activities, the plant possesses antiviral properties; however, the evaluation of the in vivo toxicity of preparations of this plant is still lacking. This study assessed the in vitro anti-HSV-1 and anti-HSV-2 activity of a crude extract (CE) obtained from the leaves of C. americana, as well as its aqueous (FAq) and ethyl-acetate fractions (FAc). In addition, the in vivo toxicity of the FAq was assessed. The sulforhodamine B method was performed to determine the antiviral activity and the in vivo toxicity was evaluated according to Brazilian federal regulations. The CE, FAq, and FAc demonstrated antiviral activity against HSV-1 in vitro, presenting EC50 values of 7.0±1.4, 1.5±0.35, and 7.5±3.8, respectively. The FAq also had activity against HSV-2 with an EC50 of 11.8±1.02. The toxicological study of FAq in animals showed that it had very low toxicity. No death occurred during acute or subchronic experiments, where up to 5000 mg/kg and 150 mg/kg FAq were tested respectively; and there were no signs of toxicity in the subchronic test. The results of this study, in conjunction with further studies, pave the way for a potential topical treatment for skin and mucosal diseases, such as HSV-1 and HSV-2 infections


2018 ◽  
Vol 92 (14) ◽  
Author(s):  
Kaiting Yang ◽  
Yong Liang ◽  
Zhichen Sun ◽  
Diyuan Xue ◽  
Hairong Xu ◽  
...  

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.


2018 ◽  
Vol 51 (1) ◽  
pp. 98-106 ◽  
Author(s):  
Min-ke Li ◽  
Yuan-yuan Liu ◽  
Fei Wei ◽  
Meng-xin Shen ◽  
Yan Zhong ◽  
...  

2017 ◽  
Vol 25 (01) ◽  
pp. 47-70
Author(s):  
CHANDRA N. PODDER ◽  
SYEDA ELHAM SHAHED ◽  
OLUWASEUN SHAROMI ◽  
SAMIR K. BHOWMIK

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.


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