VZV Infections Research Articles

Management of varicella-zoster virus infections in children.

The introduction of varicella vaccine for immunization of healthy children is expected to have a gradual impact on the incidence of VZV infections in the population but antiviral therapy remains an important intervention in clinical practice. The efficacy of aciclovir for treatment of primary and recurrent VZV infections in children has reduced the morbidity and mortality of these illnesses in immunocompromised children dramatically. Oral aciclovir is an effective and useful for the management of varicella in healthy children and adolescents.

French recommendations on the treatment of VZV infections

French recommendations on the treatment of VZV infections

Relationship of KSHV/HHV-8 Replication to Extent and Course of Kaposi's Sarcoma and Response to Therapy.

26 Objectives: To determine if KSHV/HHV-8 burden correlates with extent or progression of Kaposi's sarcoma (KS) and can predict or reflect treatment response. Methods: DNA QC PCR capable of detecting HHV-8 at the single copy level and quantitating 5 copies of HHV-8 per 106 PBMC was used to determine viral burden. KSHV message levels in PBMC samples were determined by RT PCR, using L32 ribosomal protein RNA as an internal control. Samples analyzed included PBMC: [1] a historical cross-section of KS patients, [2] PBMC from a KS/ AZT trial, [3] KS lesions treated with topical 9-cis retinoic acid (RA), and [4] PBMC from KS patients on triple-drug antiretroviral therapy. Results: KSHV/HHV-8 burden was found not to be unrelated to CD4 count, or HIV-1 plasma RNA, overall, though trends for falling HIV and HHV-8 burden were seen in patients treated with triple-drug therapy. HHV-8 burden was higher in patients with CMV, HSV, and VZV infections. Patients treated with ganciclovir or foscavir did not have lower average PBMC HHV-8 burdens. Patients without mucosal or visceral disease were found to have low to undetectable (≤5-5×102 copies/106 PBMC) PBMC burden while patients with mucosal disease or visceral disease displayed significantly higher PBMC burden (2×103-104 copies/106 PBMC). High or increasing HHV-8 burden was associated with progression of Kaposi's sarcoma. Cytotoxic chemotherapy (or αINF) and topical RA treatment reduced viral burden by an average of 80% in blood or lesions respectively. Results of message expression will be discussed. Conclusions: HHV-8 PBMC does not reflect Immunodeficiency or activity of HIV disease. HHV-8 QC PCR may show promise as a tool for both prediction of risk of progression and assessment of response in KS patients.

WS084 Treatment options for HSV and VZV infections

WS084 Treatment options for HSV and VZV infections

Acyclic nucleosides as antiviral compounds.

Acyclovir is an effective drug for the treatment of HSV and VZV infections, which after phosphorylation to the triphosphate, inhibits viral DNA polymerase. Acyclovir has low oral bioavailability, therefore prodrugs have been developed, and the L-valyl ester, valaciclovir, recently has been licensed for the treatment of shingles. Ganciclovir is used against CMV, and famciclovir, a lipophilic prodrug of penciclovir, is marketed for shingles. The acyclic nucleoside phosphonates are active against thymidine kinase-resistant viral strains. Promising analogs are PMEA (in clinical trial for the treatment of AIDS) and (S)-HPMPC (good in vivo activity against HSV, VZV, CMV, and EBV). Oligonucleotides incorporating acyclic nucleosides at the 3'-and 5'-ends, or constituted of amino acyclic nucleosides, are resistant to cleavage by nucleases and may be useful in antisense and/or antigene therapy. HEPT is active against HIV-1: It binds in a hydrophic pocket on reverse transcriptase, rather than in the polymerase active site. Some acyclic nucleosides are potent inhibitors of purine and pyrimidine nucleoside phosphorylase. These compounds may have a therapeutic niche in combination therapy with antiviral and anticancer nucleosides, and in the treatment of diseases involving the T-cell.

Varicella-Zoster Virus: Aspects of Pathogenesis and Host Response to Natural Infection and Varicella Vaccine

Events in the pathogenesis of infection and the host response to VZV are very closely linked. Our experiments demonstrate that CD4- and CD8+ T-lymphocyte populations that are targets of cell-associated VZV viremia also mediate protection against severe infection. Diminished cell-mediated immunity predisposes the host to progressive primary or recurrent VZV disease because infected lymphocytes persist in the circulation and carry the virus to major organs, causing pneumonitis, hepatitis, or other life-threatening complications. The live attenuated varicella vaccine induces cell-mediated immunity and protects against or significantly reduces the morbidity associated with primary VZV infections. The universal administration of varicella vaccine is likely to generate new insights about host-virus interactions, particularly in relation to how VZV immunity is maintained, that will be relevant to the design of vaccines for other human herpesviruses.

Efficacy of A-73209, a potent orally active agent against VZV and HSV infections

A-73209 is a novel oxetanocin derivative with potent in vitro and in vivo activity against VZV, HSV-1, and HSV-2. A-73209 was two logs more potent than acyclovir against five thymidine kinase positive (TK +) strains of VZV in vitro (mean EC 50 0.01 vs. 1.22 μg/ml). The activity of A-73209 was one log more potent than acyclovir against TK + HSV-1 strains in vitro (EC 50 = 0.03 vs. 0.32 μg/ml). A-73209 yielded a mean EC 50 of 2.2 μg/ml compared to a mean EC 50 of 0.37 μg/ml for acyclovir against a panel of TK + HSV-2 strains in vitro. The in vitro activity of A-73209 against thymidine kinase negative or deficient strains of VZV, HSV-1 and HSV-2 was much lower than for the corresponding TK + strains. A-73209 produced efficacy superior to acyclovir against lethal systemic or intracerebral HSV-1 infections in mice. The greater efficacy of A-73209 relative to acyclovir was especially apparent with oral dosing. Against HSV-2 infections in mice, the efficacy of A-73209 ranged from equal to 1.7 times less active relative to acyclovir with oral dosing. A-73209 was orally bioavailable in mice, with maximal serum concentrations well in excess of in vitro inhibitory concentrations. A-73209 appears to be a potent and selective agent against varicella-zoster virus and herpes simplex virus infections.

Antivirals for the treatment of herpesvirus infections.

Agents available to treat herpesvirus infections include idoxuridine, trifluridine, vidarabine and acyclovir for the topical treatment of herpetic eye infections; vidarabine and acyclovir for the systemic (intravenous) treatment of herpes encephalitis; acyclovir for the topical and systemic (oral) treatment of genital herpes; acyclovir for the systemic (intravenous, oral) treatment of HSV or varicella-zoster (VZV) infections in immunosuppressed patients; brivudin for the systemic (oral) treatment of HSV-1 or VZV infections in immunosuppressed patients; and ganciclovir and foscarnet for the systemic (intravenous) treatment of cytomegalovirus (CMV) retinitis in AIDS patients. Brivudin is also effective in the treatment of herpetic eye infections that no longer respond to idoxuridine, trifluridine, vidarabine or acyclovir; and foscarnet is effective in the treatment of infections with acyclovir-resistant, thymidine kinase-deficient (TK-) HSV or VZV mutants. Other antiviral agents considered for use in herpesvirus infections include brovavir, penciclovir (and its prodrug famciclovir), desciclovir (a prodrug of acyclovir), bishydroxymethylcyclobutylguanine (BHCG) and, in particular, 1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC). The latter is more active than either acyclovir or ganciclovir in the chemotherapy and prophylaxis of various HSV-1, HSV-2, TK- HSV, VZV or CMV infections in animal models.

117 Antiviral evaluation of A-73209, a potent, orally active agent against VZV and HSV infections: J. Clement 1, J. Alder 1, K. Marsh 1, D. Norbeck 1, W. Rosenbrook 1, T. Herrin 1, C. Hartline 2 and E. Kern 2. Abbott Laboratories 1, Abbott Park, IL and the University of Alabama 2, Birmingham, AL, U.S.A.

117 Antiviral evaluation of A-73209, a potent, orally active agent against VZV and HSV infections: J. Clement 1, J. Alder 1, K. Marsh 1, D. Norbeck 1, W. Rosenbrook 1, T. Herrin 1, C. Hartline 2 and E. Kern 2. Abbott Laboratories 1, Abbott Park, IL and the University of Alabama 2, Birmingham, AL, U.S.A.

Viral activity in skin lesions of herpes zoster.

AbstractVaricella‐zoster virus (VZV) was isolated in 41 of 53 (77%) patients with herpes zoster on the first to ninth days after the rash. The isolation rate was highest on the early days, as high as 86% on days one and two of rash, and gradually decreased to the ninth day; the isolation rate depended more upon the condition of skin lesions than the days of illness. The high viral activity in the rash proves its important role as the source of VZV infections and the reliability of virus isolation for the diagnosis of herpes zoster.

Chronic herpes simplex virus and varicella zoster virus infection

After defining such terms as persistent and chronic infection, latency, recurrence, recrudescence, and exogenous reinfection they are applied to infections with HSV and VZV. Possible factors determining pathogenicity are discussed, and an overview is given of the wide range of illnesses and case reports ascribed to HSV and VZV infections. Various types of infection afford different diagnostic procedures. Besides virus isolation supplemented by viral antigen identification IgG antibody tests (increase in titer) may be useful. IgG subtype and IgA antibody determinations appear to be of limited value. Despite the rather large number of available tests, there are still considerable shortcomings in their ultimate significance as to the patient's disease. Thus, some new experimental approaches are mentioned.

Sensitive analytic ELISAs for subclass herpes virus IgG

The subclass distribution of antiviral antibodies to three herpes viruses was studied in a population of healthy blood donors. Subclassification by monoclonal antibodies led to the identification of certain viral IgG patterns. IgGI appeared to be formed in response to almost all CMV, HSV-1 and VZV infections. A higher frequency of virus-specific IgG3 to CMV and HSV-1 suggested that these infections may be reactivated subclinically more often than VZV. The presence of CMV and VZV IgG4 showed a familial relationship, while IgG4 responses to HSV-1 were common. Persons with IgG4 as the only subclass-reactive antibody to CMV showed cell-related reactivities in a high frequency. Patients with leukemias, myelomas and Crohn's disease had a near-normal subclass pattern to the herpes viruses.

Serological Studies on the Antigenic Relationship between Herpes Simplex Virus and Varicella-Zoster Virus

If crossreacting antibodies between varicella-zoster virus 01ZV) and herpes simplex virus (HSV) exist, one would expect more positive reactions with VZV in a group of HSV positive patients than in a group of HSV negative patients. This statement can only apply to a group of individuals where positive and negative reactions with respect to HSV and VZV are evenly distributed. Such a distribution can only be found among children. Therefore, the relationship between HSV -1 and VZV was the only one which was considered in this investigation, since the incidence of HSV-2 antibodies in children is very rare. The sera from 197 children were examined using the neutralization test (NT), the complement fixation test (CFT) and the indirect immunofluorescent assay (1FT) and could be classified as either HSV positive (80) or HSV negative (117). The children's ages were similar in both groups. Approximately the same proportion of VZV positive sera was found in both groups when examined using 1FT (53% in the HSV positive and 47% in the HSV negative group). However, when the CFTwas applied the proportion of VZV positive sera in the two groups differed markedly (22% of the HSV positive sera and 38% of the HSV negative sera). These findings suggest that crossreactivity observed between HSV and VZV in acute HSV and VZV infections is evidently not dependent on crossreacting antibodies but is apparently confined to the cellular level of the immune response.