| an orally bioavailable antipoxvirus compound (st-246) inhibits extracellular virus formation and protects mice from lethal orthopoxvirus challenge. | st-246 is a low-molecular-weight compound (molecular weight = 376), that is potent (concentration that inhibited virus replication by 50% = 0.010 microm), selective (concentration of compound that inhibited cell viability by 50% = >40 microm), and active against multiple orthopoxviruses, including vaccinia, monkeypox, camelpox, cowpox, ectromelia (mousepox), and variola viruses. cowpox virus variants selected in cell culture for resistance to st-246 were found to have a single amino acid change ... | 2005 | 16189015 |
| efficacy of delayed treatment with st-246 given orally against systemic orthopoxvirus infections in mice. | st-246 was evaluated for activity against cowpox virus (cv), vaccinia virus (vv), and ectromelia virus (ectv) and had an in vitro 50% effective concentration (ec50) of 0.48 microm against cv, 0.05 microm against vv, and 0.07 microm against ectv. the selectivity indices were >208 and >2,000 for cv and vv, respectively. the in vitro antiviral activity of st-246 was significantly greater than that of cidofovir, which had an ec50 of 41.1 microm against cv and 29.2 microm against vv, with selectivity ... | 2007 | 17116683 |
| efficacy of therapeutic intervention with an oral ether-lipid analogue of cidofovir (cmx001) in a lethal mousepox model. | in the 21st century we are faced with the potential use of natural or recombinant varv and mpxv as biological weapons, and the emergence of human mpxv. such an occurrences would require therapeutic and prophylactic intervention with antivirals. cidofovir, an antiviral approved for the treatment of cytomegalovirus retinitis in aids patients, has activity against poxviruses, but must be administered intravenously and is associated with nephrotoxicity. an ether-lipid analogue of cdv, cmx001 (hdp-cd ... | 2008 | 17904231 |
| ly49h is necessary for genetic resistance to murine cytomegalovirus. | natural killer (nk) cells play critical roles in antiviral immunity. while the importance of effector mechanisms such as interferons has been demonstrated through knockout mice, specific mechanisms of how viruses are recognized and controlled by nk cells are less well defined. previous genetic studies have mapped the resistance genes for murine cytomegalovirus (mcmv), herpes simplex virus-1 (hsv-1), and ectromelia virus to the nk gene complex on murine chromosome 6, a region containing the polym ... | 2008 | 18668236 |
| effective post-exposure protection against lethal orthopoxviruses infection by vaccinia immune globulin involves induction of adaptive immune response. | the therapeutic potential of human vaccinia immunoglobulin (vig) in orthopoxvirus infection was examined using two mouse models for human poxvirus, based on ectromelia virus and vaccinia western reserve (wr) respiratory infections. despite the relatively fast clearance of human vig from mice circulation, a single vig injection protected immune-competent mice against both infections. full protection against lethal ectromelia virus infection was achieved by vig injection up to one day post-exposur ... | 2009 | 19195492 |
| alkoxyalkyl esters of 9-(s)-(3-hydroxy-2-phosphonomethoxypropyl) adenine are potent and selective inhibitors of hepatitis b virus (hbv) replication in vitro and in hbv transgenic mice in vivo. | alkoxyalkyl esters of acyclic nucleoside phosphonates have previously been shown to have increased antiviral activity when they are administered orally in animal models of viral diseases, including lethal infections with vaccinia virus, cowpox virus, ectromelia virus, murine cytomegalovirus, and adenovirus. 9-(s)-(3-hydroxy-2-phosphonomethoxypropyl)adenine [(s)-hpmpa] was previously shown to have activity against hepatitis b virus (hbv) in vitro. to assess the effect of alkoxyalkyl esterificatio ... | 2009 | 19398648 |
| studying nk cell responses to ectromelia virus infections in mice. | here we describe methods for the in vivo study of antiviral nk cell responses using the mouse orthopoxvirus ectromelia virus as a model, the agent of mousepox. the methods include those specific for the preparation and use of ectromelia virus such as the production of virus stocks in tissue culture and in live mice, the purification of virus stocks, the titration of virus stocks and virus loads in organs, and the infection of mice. the chapter also includes methods for the specific study of nk c ... | 2010 | 20033657 |
| age-dependent susceptibility to a viral disease due to decreased natural killer cell numbers and trafficking. | although it is well known that aged hosts are generally more susceptible to viral diseases than the young, specific dysfunctions of the immune system directly responsible for this increased susceptibility have yet to be identified. we show that mice genetically resistant to mousepox (the mouse parallel of human smallpox) lose resistance at mid-age. surprisingly, this loss of resistance is not a result of intrinsically defective t cell responses. instead, the primary reason for the loss of resist ... | 2010 | 20876312 |
| ectromelia virus infections of mice as a model to support the licensure of anti-orthopoxvirus therapeutics. | the absence of herd immunity to orthopoxviruses and the concern that variola or monkeypox viruses could be used for bioterroristic activities has stimulated the development of therapeutics and safer prophylactics. one major limitation in this process is the lack of accessible human orthopoxvirus infections for clinical efficacy trials; however, drug licensure can be based on orthopoxvirus animal challenge models as described in the "animal efficacy rule". one such challenge model uses ectromelia ... | 2010 | 21994714 |
| prevalence of viral, bacterial and parasitological diseases in rats and mice used in research environments in australasia over a 5-y period. | viral, bacterial and parasitological infections in rats and mice used in biomedical research continue to occur despite improved housing and biosurveillance. the presence of disease in laboratory animals can lead to spurious results for research undertaken in universities, research institutes and the pharmaceutical industry. here the authors report the results of serological, microbiological, parasitological and molecular tests done on mice and rats from australasia submitted to a rodent health m ... | 2011 | 22012194 |
| [orthopoxvirus genes for kelch-like proteins. iii. construction of mousepox (ectromelia) virus variants with targeted gene deletions]. | mousepox (ectromelia) virus genome contains four genes encoding for kelch-like proteins evm018, evm027, evm150 and evm167. a complete set of insertion plasmids was constructed to allow the production of recombinant ectromelia viruses with targeted deletions of one to four genes of kelch family both individually (single mutants) and in different combinations (double, triple and quadruple mutants). it was shown that deletion of any of the three genes evmo18, evm027 or evm167 resulted in reduction ... | 2009 | 19807023 |
| mousepox in the c57bl/6 strain provides an improved model for evaluating anti-poxvirus therapies. | the intranasal lethal mousepox model employing the a/ncr mouse strain is used to evaluate anti-orthopoxvirus therapies. these infections mimic large droplet transmission and result in 100% mortality within 7-10 days with as little as 1 pfu of ectromelia virus. unlike the a/ncr model, humans are less susceptible to lethal respiratory infections with variola virus and monkeypox virus as demonstrated by their lower mortality rates. in this study we show that a low dose intranasal infection of c57bl ... | 2009 | 19100593 |
| the orthopoxvirus type i ifn binding protein is essential for virulence and an effective target for vaccination. | nonliving antiviral vaccines traditionally target proteins expressed at the surface of the virion with the hope of inducing neutralizing antibodies. orthopoxviruses (opvs), such as the human smallpox virus and the mouse-equivalent ectromelia virus (ectv; an agent of mousepox), encode immune response modifiers (irms) that can increase virulence by decreasing the host immune response. we show that one of these irms, the type i interferon (ifn) binding protein (bp) of ectv, is essential for ectv vi ... | 2008 | 18391063 |
| residual active granzyme b in cathepsin c-null lymphocytes is sufficient for perforin-dependent target cell apoptosis. | cathepsin c activates serine proteases expressed in hematopoietic cells by cleaving an n-terminal dipeptide from the proenzyme upon granule packaging. the lymphocytes of cathepsin c-null mice are therefore proposed to totally lack granzyme b activity and perforin-dependent cytotoxicity. surprisingly, we show, using live cell microscopy and other methodologies, that cells targeted by allogenic cd8(+) cytotoxic t lymphocyte (ctl) raised in cathepsin c-null mice die through perforin-dependent apopt ... | 2007 | 17283185 |
| biological control of vertebrate pests using virally vectored immunocontraception. | species-specific viruses are being genetically engineered to produce contraceptive biological controls for pest animals such as mice, rabbits and foxes. the virus vaccines are intended to trigger an autoimmune response in the target animals that interferes with their fertility in a process termed virally vectored immunocontraception. laboratory experiments have shown that high levels of infertility can be induced in mice infected with recombinant murine cytomegalovirus and ectromelia virus expre ... | 2006 | 16870262 |