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1.
Molecular umbrellas: a novel class of candidate topical microbicides to prevent human immunodeficiency virus and herpes simplex virus infections 总被引:1,自引:0,他引:1 下载免费PDF全文
Madan RP Mesquita PM Cheshenko N Jing B Shende V Guzman E Heald T Keller MJ Regen SL Shattock RJ Herold BC 《Journal of virology》2007,81(14):7636-7646
2.
The cotton rat provides a novel model to study genital herpes infection and to evaluate preventive strategies 下载免费PDF全文
Yim KC Carroll CJ Tuyama A Cheshenko N Carlucci MJ Porter DD Prince GA Herold BC 《Journal of virology》2005,79(23):14632-14639
Prevention of genital herpes and other sexually transmitted infections (STI) is a critical health priority because of the overwhelming impact on women and infants and the epidemiological association with human immunodeficiency virus (HIV)/AIDS. Small animal models are essential for evaluating strategies for prevention or treatment of STI. Neither the murine nor the guinea pig model of genital herpes fully recapitulates human disease. We demonstrate that herpes simplex virus type 2 (HSV-2) readily infects inbred cotton rats (Sigmodon hispidus). Consistent infection does not require pretreatment with medroxyprogesterone, and primary disease resembles that observed in humans. The animals develop genital lesions and fully recover. During primary infection, viral DNA is also detected in liver, lungs, brain, and kidneys. Clinical self-limited recurrences occur spontaneously but may also be induced by dexamethasone. Pretreatment of cotton rats with PRO 2000 gel, a candidate vaginal microbicide being evaluated in clinical trials to prevent HSV and HIV, protects cotton rats from HSV. Together, these studies suggest that the cotton rat may provide an excellent model to study genital herpes and to evaluate preventive strategies. 相似文献
3.
Remichkova M Galabova D Roeva I Karpenko E Shulga A Galabov AS 《Zeitschrift für Naturforschung. C, Journal of biosciences》2008,63(1-2):75-81
The rhamnolipid biosurfactant PS-17 and its complex with the polysaccharide alginate, both produced by the Pseudomonas sp. S-17 strain, were studied for their antiviral activity against herpes simplex virus (HSV) types 1 and 2. They significantly inhibited the herpesvirus cytopathic effect (CPE) in the Madin-Darby bovine kidney (MDBK) cell line. The investigations were carried out according to the CPE inhibition assay protocol. The suppressive effect of the compounds on HSV replication was dose-dependent and occurred at concentrations lower than the critical micelle concentration of the surfactant. The 50% inhibitory concentration (IC50) of rhamnolipid PS-17 was 14.5 microg/ml against HSV-1 and 13 microg/ml against HSV-2. The IC50 values of the complex were 435 microg/ml for HSV-1 and 482 microg/ml for HSV-2. The inhibitory effects of the substances were confirmed by measuring the infectious virus yields with the multicycle virus growth experimental design as well: deltalog CCID50 of 1.84-2.0 against the two types of herpes simplex viruses by rhamnolipid PS-17 (20 microg/ml), and a strong reduction of the HSV-2 virus yield under the effect of the alginate complex at a concentration of 450 microg/ml. The results indicate that rhamnolipid PS-17 and its alginate complex may be considered as promising substances for the development of anti-herpetic compounds. 相似文献
4.
Efficacy and safety of a new vaginal contraceptive antimicrobial formulation containing high molecular weight poly(sodium 4-styrenesulfonate) 总被引:5,自引:0,他引:5
Zaneveld LJ Waller DP Anderson RA Chany C Rencher WF Feathergill K Diao XH Doncel GF Herold B Cooper M 《Biology of reproduction》2002,66(4):886-894
Host cell infection by sexually transmitted disease (STD)-causing microbes and fertilization by spermatozoa may have some mechanisms in common. If so, certain noncytotoxic agents could inhibit the functional activity of both organisms. High molecular mass poly(sodium 4-styrenesulfonate) (T-PSS) may be one of these compounds. T-PSS alone (1 mg/ml) or in a gel (2% or 5% T-PSS) completely prevented conception in the rabbit. Contraception was not due to sperm cytotoxicity or to an effect on sperm migration. However, T-PSS inhibited sperm hyaluronidase (IC(50) = 5.3 microg/ml) and acrosin (IC(50) = 0.3 microg/ml) and caused the loss of acrosomes from spermatozoa (85% maximal loss by 0.5 microg/ml). T-PSS (5% in gel) also reduced sperm penetration into bovine cervical mucus (73% inhibition by 1 mg gel/ml). T-PSS (5% in gel) inhibited human immunodeficiency virus (HIV; IC(50)= 16 microg gel/ml) and herpes simplex viruses (HSV-1 and HSV-2; IC(50) = 1.3 and 1.0 microg gel/ml, respectively). The drug showed high efficacy against a number of clinical isolates and laboratory strains. T-PSS (5% in gel) also inhibited Neisseria gonorrhea (IC(50) < 1.0 gel/ml) and Chlamydia trachomatis (IC(50) = 1.2 microg gel/ml) but had no effect on lactobacilli. These results imply that T-PSS is an effective functional inhibitor of both spermatozoa and certain STD-causing microbes. The noncytotoxic nature should make T-PSS safe for vaginal use. T-PSS was nonmutagenic in vitro and possessed an acute oral toxicity of >5 g/kg (rat). Gel with 10% T-PSS did not irritate the skin or penile mucosa (rabbit) and caused no dermal sensitization (guinea pig). Vaginal administration of the 5% T-PSS gel to the rabbit for 14 consecutive days caused no systemic toxicity and only mild (acceptable) vaginal irritation. T-PSS in gel form is worthy of clinical evaluation as a vaginal contraceptive HIV/STD preventative. 相似文献
5.
Three fractions of fucoidans isolated from the brown seaweed Leathesia difformis (Ee, Ec and Ea) were found to be selective antiviral agents against herpes simplex virus (HSV) types 1 and 2 and human cytomegalovirus. Fraction Ea was the most active, with IC50 values in the range 0.5-1.9 microg/ml without affecting cell viability at concentrations up to 400 microg/ml. The antiherpetic activity of Ea was assessed by three different methods, plaque reduction, inhibition of virus yield and prevention of HSV-2 induced shut-off of cell protein synthesis, demonstrating that the inhibitory effect was independent of the antiviral assay and the multiplicity of infection. The mode of action of Ea could be ascribed to an inhibitory action on virus adsorption. The fucoidans did not inhibit the blood coagulation process even at concentrations exceeding more than 100 times the IC50 value. 相似文献
6.
Mandelic acid condensation polymer: novel candidate microbicide for prevention of human immunodeficiency virus and herpes simplex virus entry 总被引:6,自引:0,他引:6 下载免费PDF全文
Herold BC Scordi-Bello I Cheshenko N Marcellino D Dzuzelewski M Francois F Morin R Casullo VM Anderson RA Chany C Waller DP Zaneveld LJ Klotman ME 《Journal of virology》2002,76(22):11236-11244
Presently marketed vaginal barrier methods are cytotoxic and damaging to the vaginal epithelium and natural vaginal flora when used frequently. Novel noncytotoxic agents are needed to protect men and women from sexually transmitted diseases. One novel candidate is a mandelic acid condensation polymer, designated SAMMA. The spectrum and mechanism of antiviral activity were explored using clinical isolates and laboratory-adapted strains of human immunodeficiency virus (HIV) and herpes simplex virus (HSV). SAMMA is highly effective against all CCR5 and CXCR4 isolates of HIV in primary human macrophages and peripheral blood mononuclear cells. SAMMA also inhibits infection of cervical epithelial cells by HSV. Moreover, it exhibits little or no cytotoxicity and has an excellent selectivity index. SAMMA, although not a sulfonated or sulfated polymer, blocks the binding of HIV and HSV to cells by targeting the envelope glycoproteins gp120 and gB-2, respectively, and also inhibits HSV entry postattachment. SAMMA is an excellent, structurally novel candidate microbicide that warrants further preclinical evaluation. 相似文献
7.
de Witte L Bobardt MD Chatterji U van Loenen FB Verjans GM Geijtenbeek TB Gallay PA 《PloS one》2011,6(5):e18917
Genital herpes is a major risk factor in acquiring human immunodeficiency virus type-1 (HIV-1) infection and is caused by both Herpes Simplex virus type 1 (HSV-1) and HSV-2. The amphipathic peptide C5A, derived from the non-structural hepatitis C virus (HCV) protein 5A, was shown to prevent HIV-1 infection but neither influenza nor vesicular stomatitis virus infections. Here we investigated the antiviral function of C5A on HSV infections. C5A efficiently inhibited both HSV-1 and HSV-2 infection in epithelial cells in vitro as well as in an ex vivo epidermal infection model. C5A destabilized the integrity of the viral HSV membrane. Furthermore, drug resistant HSV strains were inhibited by this peptide. Notably, C5A-mediated neutralization of HSV-1 prevented HIV-1 transmission. An in vitro HIV-1 transmigration assay was developed using primary genital epithelial cells and HSV infection increased HIV-1 transmigration. Treatment with C5A abolished HIV-1 transmigration by preventing HSV infection and by preserving the integrity of the genital epithelium that was severely compromised by HSV infection. In conclusion, this study demonstrates that C5A represents a multipurpose microbicide candidate, which neutralizes both HIV-1 and HSV, and which may interfere with HIV-1 transmission through the genital epithelium. 相似文献
8.
9.
Melo FL Benati FJ Roman WA de Mello JC Nozawa C Linhares RE 《Microbiological research》2008,163(2):136-139
We investigated the antiviral activity of an aliphatic nitro compound (NC) isolated from Heteropteris aphrodisiaca O. Mach. (Malpighiaceae), a Brazilian medicinal plant. The NC was tested for its antiviral activity against poliovirus type 1 (PV-1) and bovine herpes virus type 1 (BHV-1) by plaque reduction assay in cell culture. The NC showed a moderate antiviral activity against PV-1 and BHV-1 in HEp-2 cells, and the 50% inhibitory concentration (IC50) were 22.01 microg/ml (selectivity index (SI)=2.83) and 21.10 microg/ml (SI=2.95), respectively. At the highest concentration of the drug (40 microg/ml) a reduction of approximately 80% in plaque assay was observed for both viruses. The treatment of cells or virus prior to infection did not inhibit the replication of virus strains. 相似文献
10.
The nonnucleoside reverse transcriptase inhibitor UC-781 inhibits human immunodeficiency virus type 1 infection of human cervical tissue and dissemination by migratory cells 总被引:4,自引:0,他引:4 下载免费PDF全文
Fletcher P Kiselyeva Y Wallace G Romano J Griffin G Margolis L Shattock R 《Journal of virology》2005,79(17):11179-11186
11.
12.
Antiviral flavonoids from the root bark of Morus alba L 总被引:7,自引:0,他引:7
A prenylated flavonoid, moralbanone, along with seven known compounds kuwanon S, mulberroside C, cyclomorusin, eudraflavone B hydroperoxide, oxydihydromorusin, leachianone G and alpha-acetyl-amyrin were isolated from the root bark of Morus alba L. Leachianone G showed potent antiviral activity (IC(50) = 1.6 microg/ml), whereas mulberroside C showed weak activity (IC(50) = 75.4 microg/ml) against herpes simplex type 1 virus (HSV-1). Their structures were elucidated by spectroscopic methods. 相似文献
13.
For prevention of HIV infection many currently licensed anti-HIV drugs and new ones in the pipeline show potential as topically applied microbicides. While macaque models have been the gold standard for in vivo microbicide testing, they are expensive and sufficient numbers are not available. Therefore, a small animal model that facilitates rapid evaluation of potential candidates for their preliminary efficacy is urgently needed in the microbicide field. We previously demonstrated that RAG-hu humanized mouse model permits HIV-1 mucosal transmission via both vaginal and rectal routes and that oral pre-exposure chemo-prophylactic strategies could be tested in this system. Here in these proof-of-concept studies, we extended this system for topical microbicide testing using HIV-1 as the challenge virus. Maraviroc, a clinically approved CCR5 inhibitor drug for HIV treatment, was formulated as a microbicide gel at 5 mM concentration in 2.2% hydroxyl ethyl cellulose. Female RAG-hu mice were challenged vaginally with HIV-1 an hour after intravaginal application of the maraviroc gel. Our results showed that maraviroc gel treated mice were fully protected against vaginal HIV-1 challenge in contrast to placebo gel treated mice which all became infected. These findings highlight the utility of the humanized mouse models for microbicide testing and, together with the recent data from macaque studies, suggest that maraviroc is a promising candidate for future microbicide clinical trials in the field. 相似文献
14.
Jim Todd Gabriele Riedner Leonard Maboko Michael Hoelscher Helen A. Weiss Eligius Lyamuya David Mabey Mary Rusizoka Laurent Belec Richard Hayes 《PloS one》2013,8(3)
Objectives
To compare the presence and quantity of cervicovaginal HIV among HIV seropositive women with clinical herpes, subclinical HSV-2 infection and without HSV-2 infection respectively; to evaluate the association between cervicovaginal HIV and HSV shedding; and identify factors associated with quantity of cervicovaginal HIV.Design
Four groups of HIV seropositive adult female barworkers were identified and examined at three-monthly intervals between October 2000 and March 2003 in Mbeya, Tanzania: (1) 57 women at 70 clinic visits with clinical genital herpes; (2) 39 of the same women at 46 clinic visits when asymptomatic; (3) 55 HSV-2 seropositive women at 60 clinic visits who were never observed with herpetic lesions; (4) 18 HSV-2 seronegative women at 45 clinic visits. Associations of genital HIV shedding with HIV plasma viral load (PVL), herpetic lesions, HSV shedding and other factors were examined.Results
Prevalence of detectable genital HIV RNA varied from 73% in HSV-2 seronegative women to 94% in women with herpetic lesions (geometric means 1634 vs 3339 copies/ml, p = 0.03). In paired specimens from HSV-2 positive women, genital HIV viral shedding was similar during symptomatic and asymptomatic visits. On multivariate regression, genital HIV RNA (log10 copies/mL) was closely associated with HIV PVL (β = 0.51 per log10 copies/ml increase, 95%CI:0.41–0.60, p<0.001) and HSV shedding (β = 0.24 per log10 copies/ml increase, 95% CI:0.16–0.32, p<0.001) but not the presence of herpetic lesions (β = −0.10, 95%CI:−0.28–0.08, p = 0.27).Conclusions
HIV PVL and HSV shedding were more important determinants of genital HIV than the presence of herpetic lesions. These data support a role of HSV-2 infection in enhancing HIV transmissibility. 相似文献15.
Giancarlo Pizza Renato Meduuri Caterina De Vinci Lucia Scorolli Dr. Dimitri Viza 《Biotherapy》1994,8(1):63-68
Transfer Factor is a dialysable moiety obtained from immune lymphocytes. It has been successfully used for the treatment of several viral infections including labial and genital herpes. In the present study, thirty-three patients with low immune response to HSV antigens and suffering from herpes ocular infections were orally treated with HSV-specific transfer factor (TF). Their relapse index was reduced from 20.1 before treatment to 0.51 after TF administration, with only 6/33 patients relapsing. Although this is not a placebo-controlled-randomized study, the results suggest that TF specific for HSV antigens may be efficacious for preventing relapses of ocular herpes infections as has been the case with genital and labial localisations.Abbreviations CMI
Cell-mediated immunity
- CMV
Cytomegalo-virus
- EBV
Epstein-Barr virus
- HIV
Human immunodeficiency virus
- HK
Herpes keratitis
- HSV
Herpes simplex virus
- IRI
Individual relapse index
- KU
Kerato-uveitis
- LMT
Leucocyte migration test
- LST
Lymphocyte stimulation test
- MIF
Migration inhibition factor
- RHK
Relapsing herpes keratitis
- TF
Transfer factor 相似文献
16.
Anti-herpes simplex virus activity of sulfated galactans from the red seaweeds Gymnogongrus griffithsiae and Cryptonemia crenulata 总被引:3,自引:0,他引:3
Talarico LB Zibetti RG Faria PC Scolaro LA Duarte ME Noseda MD Pujol CA Damonte EB 《International journal of biological macromolecules》2004,34(1-2):63-71
This study presents the chemical composition and antiviral activity against herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) of sulfated galactan crude extracts and main fractions obtained from two red seaweeds collected in Brazil, Gymnogongrus griffithsiae and Cryptonemia crenulata. Most of the eighteen tested products, including homogeneous kappa/iota/nu carrageenan and DL-galactan hybrid, exhibited antiherpetic activity with inhibitory concentration 50% (IC50) values in the range 0.5-5.6 microg/ml, as determined in a virus plaque reduction assay in Vero cells. The galactans lacked cytotoxic effects and showed a broad spectrum of antiviral activity against HSV-1 and HSV-2. No direct virus inactivation was observed after virion treatment with the galactans. The mode of action of these compounds could be mainly ascribed to an inhibitory effect on virus adsorption. Most importantly, a significant protection against a murine vaginal infection with HSV-2 was afforded by topical treatment with the sulfated galactans. 相似文献
17.
Marie-Clotilde Bernard Véronique Barban Fabrine Pradezynski Aymeric de Montfort Robert Ryall Catherine Caillet Patricia Londono-Hayes 《PloS one》2015,10(4)
HSV-2 vaccine is needed to prevent genital disease, latent infection, and virus transmission. A replication-deficient mutant virus (dl5-29) has demonstrated promising efficacy in animal models of genital herpes. However, the immunogenicity, protective efficacy, and non-replicative status of the highly purified clinical vaccine candidate (HSV529) derived from dl5-29 have not been evaluated. Humoral and cellular immune responses were measured in mice and guinea pigs immunized with HSV529. Protection against acute and recurrent genital herpes, mortality, latent infection, and viral shedding after vaginal HSV-2 infection was determined in mice or in naïve and HSV-1 seropositive guinea pigs. HSV529 replication and pathogenicity were investigated in three sensitive models of virus replication: severe combined immunodeficient (SCID/Beige) mice inoculated by the intramuscular route, suckling mice inoculated by the intracranial route, and vaginally-inoculated guinea pigs. HSV529 immunization induced HSV-2-neutralizing antibody production in mice and guinea pigs. In mice, it induced production of specific HSV-2 antibodies and splenocytes secreting IFNγ or IL-5. Immunization effectively prevented HSV-2 infection in all three animal models by reducing mortality, acute genital disease severity and frequency, and viral shedding. It also reduced ganglionic viral latency and recurrent disease in naïve and HSV-1 seropositive guinea pigs. HSV529 replication/propagation was not detected in the muscles of SCID/Beige mice, in the brains of suckling mice, or in vaginal secretions of inoculated guinea pigs. These results confirm the non-replicative status, as well as its immunogenicity and efficacy in mice and guinea pigs, including HSV-1 seropositive guinea pigs. In mice, HSV529 produced Th1/Th2 characteristic immune response thought to be necessary for an effective vaccine. These results further support the clinical investigation of HSV529 in human subjects as a prophylactic vaccine. 相似文献
18.
In vivo role of nectin-1 in entry of herpes simplex virus type 1 (HSV-1) and HSV-2 through the vaginal mucosa 下载免费PDF全文
Linehan MM Richman S Krummenacher C Eisenberg RJ Cohen GH Iwasaki A 《Journal of virology》2004,78(5):2530-2536
Herpes simplex virus type 2 (HSV-2) is transmitted through the genital mucosa during sexual encounters. In recent years, HSV-1 has also become commonly associated with primary genital herpes. The mechanism of viral entry of HSV-1 and HSV-2 in the female genital tract is unknown. In order to understand the molecular interactions required for HSV entry into the vaginal epithelium, we examined the expression of herpesvirus entry mediator nectin-1 in the vagina of human and mouse at different stages of their hormonal cycle. Nectin-1 was highly expressed in the epithelium of human vagina throughout the menstrual cycle, whereas the mouse vaginal epithelium expressed nectin-1 only during the stages of the estrous cycle in which mice are susceptible to vaginal HSV infection. Furthermore, the ability of nectin-1 to mediate viral entry following intravaginal inoculation was examined in a mouse model of genital herpes. Vaginal infection with either HSV-1 or HSV-2 was blocked by preincubation of the virus with soluble recombinant nectin-1. Viral entry through the vaginal mucosa was also inhibited by preincubation of HSV-2 with antibody against gD. Together, these results suggest the importance of nectin-1 in mediating viral entry for both HSV-1 and HSV-2 in the genital mucosa in female hosts. 相似文献
19.
Herpes simplex virus (HSV) is one of the most common, yet frequently overlooked, sexually transmitted infections. Since the type of HSV infection affects prognosis and subsequent counseling, type-specific testing to distinguish HSV-1 from HSV-2 is recommended. Although PCR has been the diagnostic standard for HSV infections of the central nervous system, until now viral culture has been the test of choice for HSV genital infection. However, HSV PCR, with its consistently and substantially higher rate of HSV detection, will likely replace viral culture as the gold standard for the diagnosis of genital herpes in people with active mucocutaneous lesions, regardless of anatomic location or viral type. Alternatively, type-specific serologic tests based on glycoprotein G should be the test of choice to establish the diagnosis of HSV infection when no active lesion is present. Given the difficulty in making the clinical diagnosis of HSV, the growing worldwide prevalence of genital herpes and the availability of effective antiviral therapy, there is an increased demand for rapid, accurate laboratory diagnosis of patients with HSV. 相似文献
20.
Segarra TJ Fakioglu E Cheshenko N Wilson SS Mesquita PM Doncel GF Herold BC 《PloS one》2011,6(11):e27675