Modulation of the host immune response by cowpox virus

Cowpox virus, a zoonotic poxvirus endemic to Eurasia, infects a large number of host species which makes its eradication impossible. The elimination of world-wide smallpox vaccination programs renders the human population increasingly susceptible to infection by orthopoxviruses resulting in a growing number of zoonotic infections including CPXV transmitted from domestic animals to humans. The ability of CPXV to infect a wide range of mammalian host is likely due to the fact that, among the orthopoxviruses, CPXV encodes the most complete set of open reading frames expected to encode immunomodulatory proteins. This renders CPXV particularly interesting for studying poxviral strategies to evade and counteract the host immune responses.     

Effect of double infection of cowpox virus-infected cells with paramyxovirus (Sendai virus) on formation of cowpox virus-specific cell surface antigen.

The formation of cowpox virus-specific cell surface antigen (CPV S-ag) was significantly enhanced by double infection with HVJ (Sendai virus). Simultaneous double infection, superinfection with HVJ and superinfection with CPV of cells persistently infected with HVJ similarly enhanced the formation of CPV S-ag, while pre-infection with HVJ was ineffective. To be effective, cells must be infected at a m.o.i. of greater than or equal to 1.0 and HVJ gene functions had to be expressed. The HVJ-infected cell extracts had an ability to accelerate uncoating (or degradation) of CPV, causing an early increase and a subsequent decrease in the infectivity of CPV. This activity reached a maximum 4--6 hr after HVJ infection, the increase paralleling enhancement of the total activity of several cellular enzymes. Addition of puromycin abolished the increase of these activities and the formation of CPV S-ag. Thus, the double infection with HVJ of CPV-infected cells induces an enhancement of CPV S-ag formation presumably as a consequence of activation of cellular enzymes which in turn accelerates uncoating of CPV.     

Ebola virus: from discovery to vaccine

Ebola virus, being highly pathogenic for humans and non-human primates and the subject of former weapons programmes, is now one of the most feared pathogens worldwide. In addition, the lack of pre- and post-exposure interventions makes the development of rapid diagnostics, new antiviral agents and protective vaccines a priority for many nations. Further insight into the ecology, immunology and pathogenesis of Ebola virus will promote the delivery of these urgently required tools.     

A cowpox virus gene required for multiplication in Chinese hamster ovary cells.

Cowpox virus, in contrast to vaccinia virus, can multiply in Chinese hamster ovary cells. To study the genetic basis for this difference in host range, recombinants between vaccinia and cowpox viruses were isolated and their DNA restriction patterns were examined. The ability to multiply in Chinese hamster ovary cells could be correlated with the conservation of cowpox virus sequences mapping at the left end of the genome. This was further demonstrated by marker rescue of the host range phenotype with restricted cowpox virus DNA. Marker rescue with cloned restriction fragments of decreasing size enabled the fine localization of the host range function to a 2.3-kilobase-pair fragment. Nucleotide sequencing revealed that the fragment encoded a single major polypeptide of approximately 77,000 daltons. It is suggested that the role of the host range gene from cowpox virus is to prevent the early and extensive shutoff of protein synthesis that normally occurs in Chinese hamster ovary cells infected by vaccinia virus.     

Infection with cowpox virus decreases female maturation rates in wild populations of woodland rodents

Sublethal effects of parasitic infection, such as reductions in reproductive rate, can significantly affect host population dynamics. Here we show that in wild populations of both Clethrionomys glareolus (bank vole) and Apodemus sylvaticus (wood mouse), females infected with cowpox virus are likely to delay maturation and therefore reproduction – in most cases until the following breeding season. Some infected bank voles do mature in their year of birth but still take longer than uninfected females. Together with our previous demonstration that individuals infected with cowpox virus in the summer survive better than uninfected individuals, these results support the prediction that hosts that develop an acute infection may best optimise their fitness by decreasing current reproduction to maximise the probability of surviving infection. Moreover, as the proportion of individuals infected increases with density, the reduction in host fecundity may have significant consequences for host dynamics.     

Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme.

Cowpox virus effectively inhibits inflammatory responses against viral infection in the chick embryo. This study demonstrates that one of the viral genes necessary for this inhibition, the crmA gene (a cytokine response modifier gene), encodes a serpin that is a specific inhibitor of the interleukin-1 beta converting enzyme. This serpin can prevent the proteolytic activation of interleukin-1 beta, thereby suppressing an interleukin-1 beta response to infection. However, the modification of this single cytokine response is not sufficient to inhibit inflammatory responses. This suggests that cowpox virus encodes several cytokine response modifiers that act together to inhibit the release of pro-inflammatory cytokines in response to infection. These viral countermeasures to host defenses against infection may contribute significantly to the pathology associated with poxvirus infections.     

Inference of cowpox virus transmission rates between wild rodent host classes using space-time interaction

There have been virtually no studies of 'who acquires infection from whom' in wildlife populations, but patterns of transmission within and between different classes of host are likely to be reflected in the spatiotemporal distribution of infection among those host classes. Here, we use a modified form of K-function analysis to test for space-time interaction among bank voles and wood mice infectious with cowpox virus. There was no evidence for transmission between the two host species, supporting previous evidence that they act as separate reservoirs for cowpox. Among wood mice, results suggested that transmission took place primarily between individuals of the opposite sex, raising the possibility that cowpox is sexually transmitted in this species. Results for bank voles indicated that infected females might be a more important source of infection to either sex than are males. The suggestion of different modes of transmission in the two species is itself consistent with the apparent absence of transmission between species.     

Chasing the dream: plant EST microarrays

DNA microarray technology is poised to make an important contribution to the field of plant biology. Stimulated by recent funding programs, expressed sequence tag sequencing and microarray production either has begun or is being contemplated for most economically important plant species. Although the DNA microarray technology is still being refined, the basic methods are well established. The real challenges lie in data analysis and data management. To fully realize the value of this technology, centralized databases that are capable of storing microarray expression data and managing information from a variety of sources will be needed. These information resources are under development and will help usher in a new era in plant functional genomics.     

埃博拉病毒疫苗研究进展

埃博拉病毒是一种可引起人和非人灵长类动物出血热传染病的最为致命的烈性病毒,致死率可达90%。2014年在西非爆发的埃博拉疫情引起了全世界的关注。疫苗接种是预防和控制传染病最为常规和有效的方法,尽管目前还没有正式获得批准上市的埃博拉病毒疫苗,但是已有多个尚处于研究阶段的疫苗在非人灵长类动物上取得了很好的保护效果,并有几个已进入临床Ⅰ期试验阶段,有望尽快用于本次埃博拉疫情的防控。本文对目前处于研究阶段的多个类型的埃博拉病毒疫苗进行了综述,为相关研究人员提供参考。     

The effect of cowpox virus infection on fecundity in bank voles and wood mice.

Although epidemic infectious diseases are a recognized cause of changes in host population dynamics, there is little direct evidence for the effect of endemic infections on populations. Cowpox virus is an orthopoxvirus which is endemic in bank voles (Clethrionomys glareolus), wood mice (Apodemus sylvaticus) and field voles (Microtus agrestis) in Great Britain. It does not cause obvious signs of disease nor does it affect survival, but in this study we demonstrate experimentally that it can reduce the fecundity of bank voles and wood mice by increasing the time to first litter by 20-30 days. The pathogenic mechanisms causing this effect are at present not known, but this finding suggests that natural subclinical infection could have a considerable effect on the dynamics of wild populations.