3-Hydroxyphthaloyl β-Lactoglobulin. III. Antiviral Activity against Herpesviruses

1998 ◽  
Vol 9 (2) ◽  
pp. 177-184 ◽  
Author(s):  
AR Neurath ◽  
N Strick ◽  
Y-Y Li
Keyword(s):  
Antiviral Agents ◽  
Antiviral Agent ◽  
Major Protein ◽  
Compound I ◽  
Sexually Transmitted ◽  
Prophylactic Measures ◽  
Simplex Virus ◽  
Β Lactoglobulin ◽  
Hiv 1 ◽  
Hsv 1

The spread of sexually transmitted diseases, including human immunodeficiency virus type 1 (HIV-1) and herpesvirus infections, has continued unabated despite educational efforts spearheaded as a response to the HIV-1 epidemic. This suggests the need for prophylactic measures, including the application of topical antiviral agents. Chemical modification of bovine β-lactoglobulin (β-LG), the major protein of whey, by hydroxyphthalic anhydride (3HP) led to the generation of a potent HIV-1 inhibitor (designated 3HP-β-LG) shown to also have activity against herpes simplex virus types 1 and 2 (HSV-1, HSV-2). This report provides more detailed results concerning the anti-herpesvirus activity of 3HP-β-LG, indicating that this compound: (i) inhibited infection by human cytomegalovirus (HCMV), which is known to besexually transmitted; (ii) inactivated the infectivity of both HSV-1 and HSV-2; (iii) inhibited cell-to-cell transmission of HSV-1 and HSV-2; and (iv) bound to HSV-1, HSV-2 and HCMV virus particles and partially inhibited the binding of anti-glycoprotein E (gE) and anti-gC monoclonal antibodies to HSV-1 and HSV-2. The binding of 3HP-β-LG to the herpesviruses under study was inhibited by aggregated human IgG, suggesting that the respective viral Fc receptor is one of the target sites for 3HP-β-LG. In agreement with results on inhibition of HIV-1 infection, 3HP-β-LG appears to be the acid anhydride-modified protein of choice as an antiviral agent against herpesviruses.

Seroprevalence and Incidence of Sexually Transmitted Diseases in a Rural Ugandan Population

1994 ◽  
Vol 5 (5) ◽  
pp. 332-337 ◽  
Author(s):  
H U Wagner ◽  
E Van Dyck ◽  
E Roggen ◽  
A J Nunn ◽  
A Kamali ◽  
...  
Keyword(s):  
Sexually Transmitted Diseases ◽  
Rural Population ◽  
Adult Population ◽  
Treponema Pallidum ◽  
Incidence Rates ◽  
Sexually Transmitted ◽  
Simplex Virus ◽  
Hiv 1 ◽  
Active Syphilis ◽  
Hsv 1

The aim of the study was to determine in a rural population the age-and sex-specific prevalence and incidence rates of serological reactivity of 5 common sexually transmitted diseases (STDs) and their association with HIV-1 antibody status. Of the adult population of two villages (529 adults aged 15 years or more) 294 provided an adequate blood specimen both on enrolment and at 12 months. The sera were tested at 3 collaborating laboratories for antibodies against HIV-1, Treponema pallidum, Haemophilus ducreyi, Chlamydia trachomatis and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). A sample of 45 children were tested for HSV-1 and HSV-2. Seroprevalence rates in adults on enrolment were 7.8% for HIV-1, 10.8% for active syphilis, 10.4% for H. ducreyi, 66.0% for C. trachomatis, 91.2% for HSV-1 and 67.9% for HSV-2. Males were significantly more likely than females to be seropositive for H. ducreyi (15.6% versus 6.6%), but less likely to be HSV-2 antibody positive (57.0% versus 74.4%). Reactivity to H. ducreyi, C. trachomatis and HSV-2 rose with increasing age. In contrast, active syphilis showed no age trend. All STDs tended to be more common in those HIV-1 seropositive. Incidence rates over the 12 months were nil for HIV-1, 0.5% for syphilis, 1.2% for H. ducreyi, 11.3% for C. trachomatis, and 16.7% for HSV-2. The results of this exploratory study indicate that all STDs included are common in this rural population. The high HSV-2 prevalence rate among adolescents suggests that HSV-2 may be an important risk factor for HIV-1 infection. HSV-2 serology may be a useful tool to monitor sexual behaviour interventions in young people.

3-Hydroxyphthaloyl β-Lactoglobulin. IV. Antiviral Activity in the Mouse Model of Genital Herpesvirus Infection

1998 ◽  
Vol 9 (4) ◽  
pp. 69-79 ◽  
Author(s):  
H Kokuba ◽  
L Aurelian ◽  
AR Neurath
Keyword(s):  
Antiviral Activity ◽  
Mouse Model ◽  
Major Protein ◽  
Viral Glycoprotein ◽  
Lesion Development ◽  
Simultaneous Exposure ◽  
Virus Shedding ◽  
Prophylactic Measures ◽  
Β Lactoglobulin ◽  
Hsv 1

The spread of sexually transmitted infections caused by herpes simplex virus type 2 (HSV-2) has continued unabated despite educational efforts generated in response to the human immunodeficiency virus (HIV) epidemic. Given the absence of effective vaccines, this indicates the need to develop prophylactic measures such as topical antiviral agents. Chemical modification of bovine β-lactoglobulin (β-LG), the major protein of whey, by hydroxyphthalic anhydride (3HP) led to the generation of a potent HIV-1 inhibitor designated 3HP-β-LG. This agent was shown to also have antiviral activity against HSV-2 and HSV-1 in vitro. Recent studies indicate that 3HP-β-LG binds to HSV-1 virions, which, at least in part, involves the viral glycoprotein gE. Here we show that 3HP-β-LG inhibits HSV-2 infection in the mouse model of genital HSV-2 infection. Simultaneous exposure to HSV-2 and 3HP-β-LG caused a significant decrease in the proportion of infected animals (27% virus shedding, 5% lesion development and 0% fatality for 3HP-β-LG as compared to 80% shedding, 60% lesion development and 53% fatality in micetreated with PBS). The proportion of animals with HSV-2 infection after treatment with β-LG was similar to that in the PBS-treated group. Pretreatment with 3HP-β-LG formulated in a gel, which prolongs the presence of the agent in the vagina, also significantly reduced the proportion of HSV-2-infected mice (5% virus shedding, 5% lesion development and 0% fatality for 3HP-β-LG as compared to 70% shedding, 60% lesion development and 40% fatality in vehicle-treated mice). These differences were significant ( P≤0.0005, 0.002 and 0.008 for shedding, lesion development and fatality, respectively). Virus titres in the minority of mice that developed infection were similar to those in untreated mice. HSV-2 infection was not inhibited by treatment of an ongoing infection, indicating that 3HP-β-LG interferes with the initial infection. These data suggest that 3HP-β-LG may be an efficacious agent for preventing vaginal transmission of genital herpesvirus infections.

scholarly journals Antiviral Agents for the Prevention and Treatment of Herpes Simplex Virus Type-1 Infection in Clinical Oncology: A Network Meta-Analysis

2020 ◽  
Vol 17 (23) ◽  
pp. 8891
Author(s):  
Farah Wasim Aribi Al-Zoobaee ◽  
Loo Yee Shen ◽  
Sajesh K. Veettil ◽  
Divya Gopinath ◽  
Mari Kannan Maharajan ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Infections ◽  
Meta Analysis ◽  
Antiviral Agents ◽  
Antiviral Agent ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Assessment Development ◽  
Simplex Virus

Cancer therapy may be complicated and compromised by viral infections, including oral herpes simplex virus (HSV) infection. This network meta-analysis aimed to identify the best antiviral agent to prevent or treat oral HSV infection in patients being treated for cancer. A search was conducted for trials published since inception until the 10th of May 2020 in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. A network meta-analysis was performed on the data from randomized controlled trials that assessed antiviral agents for preventive or therapeutic activity vs. placebo, no treatment or any other active intervention in patients being treated for cancer. The agents were ranked according to their effectiveness in the prevention of oral HSV using surface under the cumulative ranking (SUCRA). Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess the certainty of the evidence. In total, 16 articles were included. The pooled relative risk (RR) to develop oral HSV infection in the acyclovir group was 0.17 (95% CI: 0.10, 0.30), compared to 0.22 (95% CI: 0.06, 0.77) in the valacyclovir group. Acyclovir ranked highest for the prevention of oral HSV followed by valacyclovir. Subgroup analysis with different acyclovir regimens revealed that the best regimens in terms of HSV-1 prevention were 750 mg/m2 acyclovir administered intravenously followed by 1600 mg per day orally. Acyclovir (250 mg/m2 per day) administered intravenously was the least effective against the prevention of oral HSV.

scholarly journals Antiherpesvirus Activities of (1′S,2′R)-9-{[1′,2′-Bis(hydroxymethyl)cycloprop-1′-yl]methyl}guanine (A-5021) in Cell Culture

1998 ◽  
Vol 42 (7) ◽  
pp. 1666-1670 ◽  
Author(s):  
Satoshi Iwayama ◽  
Nobukazu Ono ◽  
Yuko Ohmura ◽  
Katsuya Suzuki ◽  
Miho Aoki ◽  
...  
Keyword(s):  
Antiviral Agent ◽  
Inhibitory Effect ◽  
Clinical Isolates ◽  
Human Embryonic Lung ◽  
Growth Inhibition Assay ◽  
Varicella Zoster ◽  
Hel Cells ◽  
Simplex Virus ◽  
Short Time ◽  
Hsv 1

ABSTRACT Antiherpetic activity of (1′S,2′R)-9-{[1′,2′-bis(hydroxymethyl)cycloprop-1′-yl]methyl}guanine (A-5021) was compared with those of acyclovir (ACV) and penciclovir (PCV) in cell cultures. In a plaque reduction assay using a selection of human cells, A-5021 showed the most potent activity in all cells. Against clinical isolates of herpes simplex virus type 1 (HSV-1,n = 5) and type 2 (HSV-2, n = 6), mean 50% inhibitory concentrations (IC50s) for A-5021 were 0.013 and 0.15 μg/ml, respectively, in MRC-5 cells. Corresponding IC50s for ACV were 0.22 and 0.30 μg/ml, and those for PCV were 0.84 and 1.5 μg/ml, respectively. Against clinical isolates of varicella-zoster virus (VZV, n = 5), mean IC50s for A-5021, ACV, and PCV were 0.77, 5.2, and 14 μg/ml, respectively, in human embryonic lung (HEL) cells. A-5021 showed considerably more prolonged antiviral activity than ACV when infected cells were treated for a short time. The selectivity index, the ratio of 50% cytotoxic concentration to IC50, of A-5021 was superior to those of ACV and PCV for HSV-1 and almost comparable for HSV-2 and VZV. In a growth inhibition assay of murine granulocyte-macrophage progenitor cells, A-5021 showed the least inhibitory effect of the three compounds. These results show that A-5021 is a potent and selective antiviral agent against HSV-1, HSV-2, and VZV.

scholarly journals Susceptibility of Herpes Simplex Virus Isolated from Genital Herpes Lesions to ASP2151, a Novel Helicase-Primase Inhibitor

2012 ◽  
Vol 56 (7) ◽  
pp. 3587-3591 ◽  
Author(s):  
Kiyomitsu Katsumata ◽  
Adriana Weinberg ◽  
Koji Chono ◽  
Shoji Takakura ◽  
Toru Kontani ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Genital Herpes ◽  
Antiviral Agents ◽  
Term Treatment ◽  
Recurrent Genital Herpes ◽  
Short Term Treatment ◽  
Varicella Zoster ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTASP2151 (amenamevir) is a helicase-primase inhibitor against herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus. To evaluate the anti-HSV activity of ASP2151, susceptibility testing was performed on viruses isolated from patients participating in a placebo- and valacyclovir-controlled proof-of-concept phase II study for recurrent genital herpes. A total of 156 HSV strains were isolated prior to the dosing of patients, and no preexisting variants with less susceptibility to ASP2151 or acyclovir (ACV) were detected. ASP2151 inhibited HSV-1 and HSV-2 replication with mean 50% effective concentrations (EC50s) of 0.043 and 0.069 μM, whereas ACV exhibited mean EC50s of 2.1 and 3.2 μM, respectively. Notably, the susceptibilities of HSV isolates to ASP2151 and ACV were not altered after dosing with the antiviral agents. Taken together, these results demonstrate that ASP2151 inhibits the replication of HSV clinical isolates more potently than ACV, and HSV resistant to this novel helicase-primase inhibitor as well as ACV may not easily emerge in short-term treatment for recurrent genital herpes patients.

scholarly journals HIV-1 Replication in HIV-Infected Individuals Is Significantly Reduced When Peripheral Blood Mononuclear Cells Are Superinfected with HSV-1

2012 ◽  
Vol 2012 ◽  
pp. 1-6
Author(s):  
Taneth Yamsuwan ◽  
Chintana Chirathaworn ◽  
Pokrath Hansasuta ◽  
Parvapan Bhattarakosol
Keyword(s):  
T Lymphocytes ◽  
Viral Entry ◽  
Mononuclear Cells ◽  
Multiplicity Of Infection ◽  
Peripheral Blood Mononuclear ◽  
Healthy Donors ◽  
Immunodeficiency Virus ◽  
Simplex Virus ◽  
Hiv 1 ◽  
Hsv 1

Herpes simplex virus (HSV) can cause generalized infection in human immunodeficiency virus- (HIV-) infected patients leading to death. This study investigated HSV-1 replication in PBMCs from 25 HIV-infected individuals and 15 healthy donors and the effects of HSV-1 superinfection on HIV-1 production. Herpes viral entry mediator (HVEM) receptor on T lymphocytes was also evaluated. Our results confirmed that the number of activated (CD3+ and CD38+) T lymphocytes in HIV-infected individuals (46.51±17.54%) was significantly higher than in healthy donors (27.54±14.12%,Pvalue = 0.001) without any significant differences in HVEM expression. Even though the percentages of HSV-1 infected T lymphocytes between HIV-infected individuals (79.25±14.63%) and healthy donors (80.76±7.13%) were not different (Pvalue = 0.922), yet HSV-1 production in HIV-infected individuals (47.34±11.14×103 PFU/ml) was significantly greater than that of healthy donors (34.17±8.48×103 PFU/ml,Pvalue = 0.001). Moreover, HSV-1 virions were released extracellularly rather than being associated with the cells, and superinfection of HSV-1 at a multiplicity of infection (MOI) of 5 significantly decreased HIV production (Pvalue < 0.001).

scholarly journals Activity of Penciclovir in Combination with Azido-Thymidine, Ganciclovir, Acyclovir, Foscarnet and Human Interferons against Herpes Simplex Virus Replication in Cell Culture

1992 ◽  
Vol 3 (2) ◽  
pp. 85-94 ◽  
Author(s):  
D. Sutton ◽  
J. Taylor ◽  
T. H. Bacon ◽  
M. R. Boyd
Keyword(s):  
Cell Culture ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Antiviral Agents ◽  
High Concentrations ◽  
Simplex Virus ◽  
Hsv 1

Combinations of penciclovir (PCV) with other antiviral agents (acyclovir, ACV; ganciclovir, GCV; foscarnet, PFA; azido-thymidine, AZT) or with human interferons (HulFN-α,β,γ) were tested for inhibitory activity against herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) in cell culture. The antiviral interactions observed between combinations of PCV with ACV or GCV were purely additive. Combinations of PCV with HulFNs demonstrated highly synergistic anti-herpesvirus activity; some synergy was also detected between PCV and PFA against HSV-1. High concentrations of AZT inhibited the antiviral activity of PCV; this antagonism was competitive. In more detailed studies it was demonstrated that high concentrations of AZT also inhibited the antiviral activity of ACV, and that ACV was more sensitive to this antagonism than PCV. It was concluded that the antagonism was unlikely to have clinical significance.

scholarly journals Type I Interferons in Newborns—Neurotoxicity versus Antiviral Defense

mBio ◽  
2016 ◽  
Vol 7 (3) ◽  
Author(s):  
Dusan Bogunovic
Keyword(s):  
Herpes Simplex ◽  
Antiviral Agent ◽  
Type I Interferons ◽  
Age Difference ◽  
Anatomical Site ◽  
Type I ◽  
Herpes Simplex Virus 1 ◽  
Replication Control ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT In most children and adults, primary infection with herpes simplex virus 1 (HSV-1) is asymptomatic. However, very rarely (incidence of 1 in 1,000,000), it can cause herpes simplex encephalitis (HSE). HSE also occurs in infants but with a much starker incidence of one in three. This age difference in susceptibility to HSV-1-caused HSE is not well understood. In a recent article in mBio , authors have identified the choroid plexus as the anatomical site of robust HSV-1 replication in the brain. They point to low levels of type I interferon (IFN) receptor as causal of the lack of HSV-1 replication control in neonates, in contrast to adults. Here, I discuss these findings in the context of human genetic evidence. I point to the balancing act of type I IFN acting as a neurotoxin and an antiviral agent, an evolutionary choice of a lesser evil.

scholarly journals Analysis of Select Herpes Simplex Virus 1 (HSV-1) Proteins for Restriction of Human Immunodeficiency Virus Type 1 (HIV-1): HSV-1 gM Protein Potently Restricts HIV-1 by Preventing Intracellular Transport and Processing of Env gp160

2017 ◽  
Vol 92 (2) ◽  
Author(s):  
Sachith Polpitiya Arachchige ◽  
Wyatt Henke ◽  
Ankita Pramanik ◽  
Maria Kalamvoki ◽  
Edward B. Stephens
Keyword(s):  
Human Immunodeficiency Virus ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Human Immunodeficiency Virus Type ◽  
Herpes Simplex Virus 1 ◽  
Immunodeficiency Virus ◽  
Simplex Virus ◽  
Hiv 1 ◽  
Hsv 1

ABSTRACTVirus-encoded proteins that impair or shut down specific host cell functions during replication can be used as probes to identify potential proteins/pathways used in the replication of viruses from other families. We screened nine proteins from herpes simplex virus 1 (HSV-1) for the ability to enhance or restrict human immunodeficiency virus type 1 (HIV-1) replication. We show that several HSV-1 proteins (glycoprotein M [gM], US3, and UL24) potently restricted the replication of HIV-1. Unlike UL24 and US3, which reduced viral protein synthesis, we observed that gM restriction of HIV-1 occurred through interference with the processing and transport of gp160, resulting in a significantly reduced level of mature gp120/gp41 released from cells. Finally, we show that an HSV-1 gM mutant lacking the majority of the C-terminal domain (HA-gM[Δ345-473]) restricted neither gp160 processing nor the release of infectious virus. These studies identify proteins from heterologous viruses that can restrict viruses through novel pathways.IMPORTANCEHIV-1 infection of humans results in AIDS, characterized by the loss of CD4+T cells and increased susceptibility to opportunistic infections. Both HIV-1 and HSV-1 can infect astrocytes and microglia of the central nervous system (CNS). Thus, the identification of HSV-1 proteins that directly restrict HIV-1 or interfere with pathways required for HIV-1 replication could lead to novel antiretroviral strategies. The results of this study show that select viral proteins from HSV-1 can potently restrict HIV-1. Further, our results indicate that the gM protein of HSV-1 restricts HIV-1 through a novel pathway by interfering with the processing of gp160 and its incorporation into virus maturing from the cell.

scholarly journals Aetiology of sexually transmitted infections in Maputo, Mozambique

2010 ◽  
Vol 5 (01) ◽  
pp. 041-047 ◽  
Author(s):  
Tomas Francisco Zimba ◽  
Teke Apalata ◽  
Willem Adrian Sturm ◽  
Prashini Moodley
Keyword(s):  
Vaginal Discharge ◽  
Genital Ulcer ◽  
Transmitted Infection ◽  
Syndromic Management ◽  
Sexually Transmitted ◽  
Genital Ulcers ◽  
Simplex Virus ◽  
Syphilis Serology ◽  
Hiv 1

Introduction: The study sought to ascertain the prevalence of the aetiological agents of genital discharge and genital ulcer diseases in Maputo, Mozambique. Methodology: Consecutive consenting patients presenting to the Centro de Saúde do Porto in Maputo between March and April 2005 with genital discharge syndrome and/or genital ulcer diseases were recruited.  Specimens were collected for the identification of STI pathogens. Results: Of 346 recruited patients, 164 were male and 182 female. The prevalence of confirmed single aetiological agents for male urethritis was as follows: N. gonorrhoeae, 35%; C. trachomatis, 10%; and M. genitalium 4%. For vaginal discharge, N. gonorrhoeae was found in11% of the women tested, followed by C. trachomatis (6.5%), bacterial vaginosis (34%), and T. vaginalis (2%). The prevalence of genital ulcers was as follows: Herpes simplex virus type 2, 62%; H. ducreyi 4 %; and C. trachomatis biovar LGV, 4%. Five percent of patients with genital ulcers had a positive syphilis serology (RPR ≥ 1:8 and confirmed by TPHA) and 35% of all tested patients were HIV-1/2 infected. Cases of mixed infections were present in 5%, 11% and 3% of patients with male urethritis, vaginal discharge, and genital ulcers respectively.   Conclusion: The classic sexually transmitted infection aetiologies are still prevalent in Maputo. The study highlights the need for a periodic surveillance to inform syndromic management protocols. 

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