Characterization of Wild-Type and Cidofovir-Resistant Strains of Camelpox, Cowpox, Monkeypox, and Vaccinia Viruses

Smee, Donald F.; Sidwell, Robert W.; Kefauver, Debbie; Bray, Mike; Huggins, John W.

doi:10.1128/aac.46.5.1329-1335.2002

Cited by 124 publications

(107 citation statements)

References 31 publications

Supporting

Mentioning

100

Contrasting

Order By: Relevance

“…In the case of CDV, EC 50 values from previous reports record a wider range of values: 8.2 µM [Copenhagen strain in human embryonic lung cells (Neyts et al, 2002)], 12.7 µM [Lederle strain in primary human keratinocytes (Snoeck et al, 2002)], 10.1 and 13.4 µM [versus NYC and IHD strains, respectively, in human foreskin fibroblasts culture (Kern et al, 2002)] and 32-46µM for Elstree, WR, Copenhagen and NYC strains in human foreskin fibroblasts (Kern et al, 2002;Keith et al, 2003). Similar data were obtained by the plaque-reduction assay, Smee et al, 2002). In our study, EC 50 values ranged from 7.1-26.5 µM and were strongly dependent on the virus inoculum size (Table 1).…”

Section: Discussionsupporting

confidence: 71%

“…©2006 International Medical Press monkeypox, camelpox and smallpox viruses (Kern et al, 2002;Smee et al, 2002); it has shown to strongly inhibit orthopoxvirus infection in vivo, including cowpox and VV infections in mice (Neyts & De Clercq, 1993;Roy et al, 2003), and demonstrates a marked activity in mice with respiratory cowpox virus infection when prescribed as a combined treatment with ribavirin (Smee et al, 2000). More recently, CDV has been approved for the treatment of molluscum contagiosum and orf infections in humans (Silverberg, 2003;McCabe et al, 2003), and has demonstrated a marked protective effect in variola and monkeypox infection in cynomolgus monkeys (Huggins et al, 2004).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Synergistic Combination Effect of Cidofovir and Idoxuridine on Vaccinia Virus Replication

Remichkova

Petrov

Galabov

2006

Antivir Chem Chemother

View full text Add to dashboard Cite

In view of the potential menace of a terrorism attack with smallpox virus, an intensive search of chemotherapeutic agents active against orthopoxviruses is underway. We comparatively studied the antiviral activity of cidofovir (CDV) and idoxuridine (IUdR) against two vaccinia virus (VV) strains, Bratislava and RIIPD, in cell cultures of chick embryo fibroblasts (CEF). The investigations were carried out according to cytopathic effect (CPE) inhibition assay protocols. To determine the cytotoxicity of the compounds, maximal tolerated concentration (MTC) was calculated in CEF cell monolayers and 50% cell growth inhibitory concentration (CGIC 50 ) was calculated in growing cell cultures. It was found that the antiviral effects were strongly dependent on virus inoculum size. There were no marked differences in the susceptibility to CDV and IUdR between the two VV strains. The individual half maximal inhibitory concentration (IC 50 ) for CDV varied from 7.1-8.5 µ µM at 10/100 virus 50% infectious dose (ID 50 ) to 13.6-26.5 µ µM Smallpox (variola) is among the most dangerous and highly contagious viral infections affecting humans. The last natural case in Somalia has marked the end of a successful WHO campaign for smallpox eradication by vaccination on a worldwide scale (Deria et al., 1972;Fenner et al., 1988). As a result, the smallpox virus can only be found in laboratories in Atlanta, Georgia, USA and Novosibirsk, Siberia, Russia. Despite smallpox eradication, infections caused by other members of the poxvirus family are also important for human health. The monkeypox virus can infect humans and occasional cases have been reported in Equatorial Africa (Heiner et al., 1998). Molluscum contagiosum and orf infections occur in immunocompromised patients (Kuhl et al., 2003;Murray, 2004). In addition, it has been highlighted that people not vaccinated with vaccinia virus (VV) could become the target of a potential terrorist attack with smallpox (Mahy, 2003). Therefore, there is a need to renew the search of chemotherapeutical agents active against poxviruses.Poxviruses encode a large number of enzymes including DNA polymerase and thymidine kinase, which are of potential interest as targets for antiviral compounds (Citarella et al., 1972;Kit et al., 1977). The first compound described in the literature was p-amino-benzaldehyde thiosemicarbazone, which Brownlee and Hamre (1951) established inhibited the replication of VV. Bauer and Sadler (1960) found 1-methyl-1H-indole-2,3-dione-3-thiosemicarbazone (methisazone, Marboran ® ) manifested a prophylactic and not a therapeutic effect against smallpox. Later, Borysiewicz et al., (1977) found a comparatively low selectivity ratio value for 1-methyl-1H-indole-2,3-dione-3-thiosemicarbazone based on its marked immunotoxicity. Among compounds showing an anti-poxvirus activity are idoxuridine (IUdR), ribavirin, cidofovir (CDV), interferon and polyacrylic acid (De Clercq, 2001).CDV is an acyclic nucleoside phosphonate licensed for the treatment of cytomegalovirus retinitis in AIDS pat...

show abstract

Section: Discussionsupporting

confidence: 71%

mentioning

confidence: 99%

Synergistic Combination Effect of Cidofovir and Idoxuridine on Vaccinia Virus Replication

Remichkova

Petrov

Galabov

2006

Antivir Chem Chemother

View full text Add to dashboard Cite

show abstract

“…The origin, propagation, and harvest procedures for these viruses are documented elsewhere (3,31). Our studies also included 11 monkeypox-human virus isolates obtained from clinical samples during the 1996 outbreak in the Congo (unpublished data) and four cidofovirresistant orthopox virus DNAs (32). Variola virus infectious titers were determined by the plaque assay and were between 10 8 and 10 10 PFU per ml.…”

Section: Methodsmentioning

confidence: 99%

Smallpox and pan -Orthopox Virus Detection by Real-Time 3′-Minor Groove Binder TaqMan Assays on the Roche LightCycler and the Cepheid Smart Cycler Platforms

Kulesh¹,

Baker²,

Loveless³

et al. 2004

J Clin Microbiol

124

108

View full text Add to dashboard Cite

We designed, optimized, and extensively tested several sensitive and specific real-time PCR assays for rapid detection of both smallpox and pan-orthopox virus DNAs. The assays are based on TaqMan 3-minor groove binder chemistry and were performed on both the rapid-cycling Roche LightCycler and the Cepheid Smart Cycler platforms. The hemagglutinin (HA) J7R, B9R, and B10R genes were used as targets for the variola virus-specific assays, and the HA and DNA polymerase-E9L genes were used as targets for the pan-orthopox

show abstract

“…A clone of wild-type cowpox virus (Brighton strain) that produces syncytia in cell culture [8] was isolated at the U.S. Army Medical Research Institute of Infectious Diseases (Ft. Detrick, Frederick, MD, USA). This virus is designated as a syncytium-forming (SF) cowpox virus.…”

Section: Virusmentioning

confidence: 99%

“…The work was facilitated by the discovery that low (5-μl) volume i.n. infections with a syncytium-forming cowpox virus strain (the strain of virus was first described by Smee et al [8]) confines the infection primarily to the upper respiratory tract, yet is sufficient to kill mice. Various features of the pathogenesis of the low, compared to high, virus inoculum models using the same dose of infecting virus are characterized, and the effects of cidofovir treatment on the infections are presented.…”

Section: Introductionmentioning

confidence: 99%

Differential pathogenesis of cowpox virus intranasal infections in mice induced by low and high inoculum volumes and effects of cidofovir treatment

Smee

Gowen

Wandersee

et al. 2008

International Journal of Antimicrobial Agents

Self Cite

View full text Add to dashboard Cite

The causes of death from intranasal cowpox virus infections in mice remain unclear. Hypotheses include severe pneumonitis, hepatitis, and/or hyperproduction of cytokines and chemokines. This work explores these hypotheses by studying the influence of low and high volume virus inoculums on viral pathogenesis. BALB/c mice were infected intranasally with a syncytium-forming variant of cowpox virus in 5-μl or 50-μl volumes containing the same infectious virus challenge dose. The 50-μl infection produced a more rapidly lethal disease associated with severe pneumonitis, high lung and nasal virus titers, and increases in cytokine and chemokine levels in lungs and nasal tissue, while liver infection was minimal. The 5-μl inoculum infection was also lethal, but the infection was primarily confined to the upper respiratory tract, and included elevated nasal cytokine and chemokine levels. The pro-inflammatory cytokine, interleukin-6, was particularly high in both infections. Treatment of the infections with cidofovir (100 mg/kg/day for 2 days starting 24 h after virus exposure) led to survival and suppression of tissue virus titers. Treatment reduced pneumonitis in the 50-μl infection, and lessened cytokine hyperproduction in both infections. We conclude that 5-μl volume inoculum of cowpox virus causes a lethal upper respiratory tract infection, while the 50-μl inoculum targets both upper and lower respiratory tracts, with excessive release of systemic proinflammatory factors occurring. Cidofovir effectively treated both infections and slowed viral replication sufficiently to subdue the exaggerated release of pro-inflammatory mediators.

show abstract

Characterization of Wild-Type and Cidofovir-Resistant Strains of Camelpox, Cowpox, Monkeypox, and Vaccinia Viruses

Cited by 124 publications

References 31 publications

Synergistic Combination Effect of Cidofovir and Idoxuridine on Vaccinia Virus Replication

Synergistic Combination Effect of Cidofovir and Idoxuridine on Vaccinia Virus Replication

Smallpox and pan -Orthopox Virus Detection by Real-Time 3′-Minor Groove Binder TaqMan Assays on the Roche LightCycler and the Cepheid Smart Cycler Platforms

Differential pathogenesis of cowpox virus intranasal infections in mice induced by low and high inoculum volumes and effects of cidofovir treatment

Contact Info

Product

Resources

About