Susceptibility of Human Herpesvirus 6 to Acyclovir and Ganciclovir

Russler, SusanK.; Tapper, MarkA.; Carrigan, Donald R.

doi:10.1016/s0140-6736(89)90555-2

Cited by 46 publications

(16 citation statements)

References 5 publications

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“…This result may be due to the lower cytotoxicity of S2242 to CBMC than HSB-2 cells. GCV also proved to be a rather potent inhibitor of HHV-6 (EC so : 1.7 [1M for HHV-6A, 1.9 [1M for HHV-6B; SI: 94 and 84, respectively).This result is consistent with the data of others (Russler et al, 1989;Burns and Sandford, 1990). GCVis known to be phosphorylated by a gene product of HCMV-UL97 in HCMV-infected cells (Littler et al, 1992;Sullivan et al, 1992).…”

Section: Discussionsupporting

confidence: 87%

“…Other nucleoside analogues were not active at subtoxic concentrations. In this MTT assay, acyclovir (ACV), which was previously reported to be inhibitory to HHV-6-infected CBMC (Agut et al, 1989;Russler et al, 1989;Burns and Sandford, 1990), did not show any inhibitory effect on HHV-6. To increase the sensitivity and accuracy of antiviral assays for HHV-6 and also HHV-7, we have newly developed an EIA screening method based on the inhibitory effects of compounds on expression of HHV-6 late antigen (gB) in CBMC.…”

Section: Inhibitory Effects Of Nucleoside and Nucleotide Analogues Onmentioning

confidence: 85%

“…In vitro anti-HHV-6 activity of nucleoside analogues that are effective against other herpesviruses has been reported in various assay systems (Streicher et al, 1988;Agut et al, 1989Agut et al, , 1991Russler et al, 1989;Burns and Sandford, 1990;Reymen et al, 1995). These assay systems include dot blot hybridization, immunofluorescence (IF), microscopical examination of virus-induced cytopathic effect (CPE) and flow cytometry.…”

Section: Introductionmentioning

confidence: 99%

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Selective Activity of Various Nucleoside and Nucleotide Analogues against Human Herpesvirus 6 and 7

Takahashi

Suzuki

Iwata

et al. 1997

Antivir Chem Chemother

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SummaryWe have developed a new sensitive enzyme immunoassay (EIA) and MIT (tetrazolium salt) assay for screening compounds against two variants of human herpesvirus 6 (HHY-6A, HHY-6B) and human herpesvirus 7 (HHY-7) and evaluated the anti-HHY-6 and HHY-7 activity oFa series of anti-herpesvirus compounds and acyclic nucleoside phosphonate analogues. The results indicate that the pattern of activity of these compounds against these betaherpesviruses is similarto that for human cytomegalovirus (HCMY). The highest potency and selectivity against the twovariants of HHY-6 and HHY-7 was demonstrated by 52242 (N7-isomer of 6-deoxy-ganciclovir). Also, ganciclovir (GCYL foscarnet, (phosphonoformic acid; PFA) and the acyclic nucleoside phosphonate analogues such as cidofovir (HPMPq exhibited selective inhibitory activity against these viruses. Thymidine kinase (TK)-dependent drugs (acyclovir, ACY; brivudin, BYDU; and sorivudine, BYaraU) showed little, ifany, activity. These results suggest a structural homology of the DNApolymerase and a lack of TK gene among these three betaherpesviruses (HHY-6, HHY-7 and HCMY). Thefinding that HHY-7 was highly sensitive to GCY also suggests that HHY-7 may have an HCMY-UL97-homologue gene for the phosphorylation of GCY. The present EIA method is more rapid and sensitive than the previously reported procedures and could be useful for the large-scale screening of compounds against HHY-6 and HHY-7.

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Section: Discussionsupporting

confidence: 87%

Section: Inhibitory Effects Of Nucleoside and Nucleotide Analogues Onmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

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Selective Activity of Various Nucleoside and Nucleotide Analogues against Human Herpesvirus 6 and 7

Takahashi

Suzuki

Iwata

et al. 1997

Antivir Chem Chemother

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“…Current data on antiviral efficacy, although overwhelmingly suggestive of the susceptibility of HHV-6 and HHV-7 to the drugs used for the treatment of CMV infection, are conflicting. [61][62][63][64] Whereas in vitro studies suggest that ganciclovir, cidofovir, and foscarnet are effective and acyclovir has limited activity for the treatment of HHV-6 infection, there is a scarcity of data supporting their efficacy in vivo. In a case series of four patients, 39 the use of ganciclovir or foscarnet led to the recovery of HHV-6 -induced myelosuppression in three of the four patients.…”

Section: Prevention and Treatmentmentioning

confidence: 99%

The impact of human herpesvirus-6 and -7 infection on the outcome of liver transplantation

Razonable

Payá

2002

Liver Transplantation

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Human herpesvirus (HHV)-6 and -7 are novel members of the ␤-herpesvirus family that maintain latency in the human host after primary infection. Reactivation from latency and/or increased degree of viral replication occurs during periods of immune dysfunction. The clinical effect of HHV-6 and HHV-7 reactivation in recipients of liver transplants is now being recognized. Clinical illnesses such as fever, rash, pneumonitis, encephalitis, hepatitis, and myelosuppression have been described in a number of anecdotal reports. Moreover, a growing body of evidence suggests that the more important effect of HHV-6 and HHV-7 reactivation on the outcomes of liver transplantation may be mediated indirectly by their interactions with the other ␤-herpesvirus-cytomegalovirus (CMV). Coinfection among these three ␤-herpesviruses in clinical syndromes that were classically ascribed to be solely caused by CMV has been shown and has raised substantial interest in the potential role of HHV-6 and HHV-7 as copathogens in the direct and indirect illnesses caused by CMV. This article reviews the current scientific data on the role and the magnitude of impact of HHV-6 and HHV-7 infection on the outcomes of liver transplantation. (Liver Transpl 2002;8:651-658.)

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“…9,32,33 From this point of view, the observation that patients who developed HHV-6-associated diseases or those with lymphocytopenia had persistent HHV-6 DNAemia is of importance, since it may serve as a marker for initiating and monitoring of antiviral therapy.…”

Section: Discussionmentioning

confidence: 99%

Human herpesvirus 6 infection inhibits specific lymphocyte proliferation responses and is related to lymphocytopenia after allogeneic stem cell transplantation

Wang

Linde

Dahl

et al. 1999

Bone Marrow Transplant

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Summary:Human herpesvirus 6 (HHV-6) infection and the HHV-6-specific lymphocyte proliferation response were studied longitudinally in 24 patients in the first 3 months after allogeneic stem cell transplantation (allo-SCT). HHV-6 DNAemia was analyzed by a nested PCR method, and the HHV-6-specific lymphocyte proliferation responses were evaluated with a standard lymphocyte proliferation assay. All patients who responded to HHV-6 GS (variant A) antigen also responded to HHV-6 Z29 (variant B) antigen, and a response to HHV-6 Z29 antigen was detected more often than to HHV-6 GS antigen after allo-SCT (P = 0.048). HHV-6 DNA was detected in more patients after than before transplantation (P = 0.01) and in more patients with acute GVHD grades II-IV than those without (P = 0.009). An HHV-6-specific proliferative response was more often detected in patients without, than in those with persistent HHV-6 infection (three consecutively positive PBL samples; P Ͻ 0.001). Patients with persistent HHV-6 infection had lower lymphocyte counts from the 8th week after transplantation than those without (P = 0.03). No HHV-6-specific proliferation responses were detected in the three patients who developed HHV-6 disease. HHV-6 infection was associated with persistent lymphocytopenia and might thereby inhibit immune function.

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Susceptibility of Human Herpesvirus 6 to Acyclovir and Ganciclovir

Cited by 46 publications

References 5 publications

Selective Activity of Various Nucleoside and Nucleotide Analogues against Human Herpesvirus 6 and 7

Selective Activity of Various Nucleoside and Nucleotide Analogues against Human Herpesvirus 6 and 7

The impact of human herpesvirus-6 and -7 infection on the outcome of liver transplantation

Human herpesvirus 6 infection inhibits specific lymphocyte proliferation responses and is related to lymphocytopenia after allogeneic stem cell transplantation

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