Vaccinia virus and Cowpox virus are not susceptible to the interferon-induced antiviral protein MxA
6
Citation
45
Reference
10
Related Paper
Citation Trend
Abstract:
MxA protein is expressed in response to type I and type III Interferon and constitute an important antiviral factor with broad antiviral activity to diverse RNA viruses. In addition, some studies expand the range of MxA antiviral activity to include particular DNA viruses like Monkeypox virus (MPXV) and African Swine Fever virus (ASFV). However, a broad profile of activity of MxA to large DNA viruses has not been established to date. Here, we investigated if some well characterized DNA viruses belonging to the Poxviridae family are sensitive to human MxA. A cell line inducibly expressing MxA to inhibitory levels showed no anti-Vaccinia virus (VACV) virus activity, indicating either lack of susceptibility of the virus, or the existence of viral factors capable of counteracting MxA inhibition. To determine if VACV resistance to MxA was due to a virus-encoded anti-MxA activity, we performed coinfections of VACV and the MxA-sensitive Vesicular Stomatitis virus (VSV), and show that VACV does not protect VSV from MxA inhibition in trans. Those results were extended to several VACV strains and two CPXV strains, thus confirming that those Orthopoxviruses do not block MxA action. Overall, these results point to a lack of susceptibility of the Poxviridae to MxA antiviral activity.Keywords:
Cowpox virus
Poxviridae
Orthopoxvirus
Cowpox
DNA virus
Antiviral protein
Cowpox virus (CPXV) is described as the source of the first vaccine used to prevent the onset and spread of an infectious disease. It is one of the earliest described members of the genus Orthopoxvirus, which includes the viruses that cause smallpox and monkeypox in humans. Both the historic and current literature describe "cowpox" as a disease with a single etiologic agent. Genotypic data presented herein indicate that CPXV is not a single species, but a composite of several (up to 5) species that can infect cows, humans, and other animals. The practice of naming agents after the host in which the resultant disease manifests obfuscates the true taxonomic relationships of "cowpox" isolates. These data support the elevation of as many as four new species within the traditional "cowpox" group and suggest that both wild and modern vaccine strains of Vaccinia virus are most closely related to CPXV of continental Europe rather than the United Kingdom, the homeland of the vaccine.
Cowpox virus
Cowpox
Monkeypox
Orthopoxvirus
Poxviridae
Louse
Modified vaccinia Ankara
Cite
Citations (108)
During the last decades, cowpox virus, a member of the genus Orthopoxvirus within the Poxviridae family, has appeared as a pathogen in domestic cats, zoo animal species, and humans. At the same time, vaccinia virus, another orthopoxvirus, has been used as a recombinant vaccine vector with foreign genes inserted in the thymidine kinase (TK) gene. By PCR and cycle sequencing, we have determined the nucleotide sequences of the TK gene and the A‐type inclusion protein (ATIP) gene of virus isolates from two human cowpox cases in Sweden, as well as a human and a feline case from Norway. We also obtained the corresponding sequences from ectromelia virus (strain Moscow), cow‐pox virus (strain Brighton) and vaccinia virus (strain Western Reserve). The new virus isolates differed from ectromelia virus and vaccinia virus, and were confirmed to be cowpox virus strains. Isolates originating from the same country had nearly identical TK sequences and fully identical ATIP sequences. They probably represent local geographical strains of cowpox virus.
Cowpox virus
Ectromelia virus
Orthopoxvirus
Cowpox
Poxviridae
Recombinant virus
Fowlpox virus
Cite
Citations (10)
Funding sources: none. Conflicts of interest: none declared. Madam, Cowpox virus belongs to the family of Poxviridae, genus Orthopoxvirus, and is closely related to smallpox, vaccinia and monkeypox virus.1 Human cowpox is a zoonotic infection transmitted by mouse‐hunting cats or pet rats having their reservoir in wild rodents.2 The confusing names of cowpox and the closely related vaccinia virus originate from 1776 when Edward Jenner inoculated material from a dairymaid's hand to a boy who was subsequently protected against smallpox. Jenner described the difficulties of finding appropriate cowpox lesions in cows, suitable for vaccination.3 In fact, cows were later shown to be only accidental hosts of cowpox virus.4 In immunocompetent individuals, cowpox show a self‐healing disease with usually one painful lesion that passes the stages of a macule, papule or nodule, vesicle, pustule, ulcer and eschar with surrounding erythema and oedema.1 In contrast, in immunodeficient or eczematous patients, cowpox infection may become generalized, be accompanied with systemic symptoms or even be fatal.5, 6
Cowpox
Cowpox virus
Orthopoxvirus
Poxviridae
Monkeypox
Papule
Variola virus
Eschar
Lymphangitis
Cite
Citations (30)
Abstract Background Animal-borne orthopoxviruses, like monkeypox, vaccinia and the closely related cowpox virus, are all capable of causing zoonotic infections in humans, representing a potential threat to human health. The disease caused by each virus differs in terms of symptoms and severity, but little is yet know about the reasons for these varying phenotypes. They may be explained by the unique repertoire of immune and host cell modulating factors encoded by each virus. In this study, we analysed the specific modulation of the host cell’s gene expression profile by cowpox, monkeypox and vaccinia virus infection. We aimed to identify mechanisms that are either common to orthopoxvirus infection or specific to certain orthopoxvirus species, allowing a more detailed description of differences in virus-host cell interactions between individual orthopoxviruses. To this end, we analysed changes in host cell gene expression of HeLa cells in response to infection with cowpox, monkeypox and vaccinia virus, using whole-genome gene expression microarrays, and compared these to each other and to non-infected cells. Results Despite a dominating non-responsiveness of cellular transcription towards orthopoxvirus infection, we could identify several clusters of infection-modulated genes. These clusters are either commonly regulated by orthopoxvirus infection or are uniquely regulated by infection with a specific orthopoxvirus, with major differences being observed in immune response genes. Most noticeable was an induction of genes involved in leukocyte migration and activation in cowpox and monkeypox virus-infected cells, which was not observed following vaccinia virus infection. Conclusion Despite their close genetic relationship, the expression profiles induced by infection with different orthopoxviruses vary significantly. It may be speculated that these differences at the cellular level contribute to the individual characteristics of cowpox, monkeypox and vaccinia virus infections in certain host species.
Cowpox virus
Orthopoxvirus
Cowpox
Poxviridae
Monkeypox
Variola virus
Cite
Citations (58)
MxA protein is expressed in response to type I and type III Interferon and constitute an important antiviral factor with broad antiviral activity to diverse RNA viruses. In addition, some studies expand the range of MxA antiviral activity to include particular DNA viruses like Monkeypox virus (MPXV) and African Swine Fever virus (ASFV). However, a broad profile of activity of MxA to large DNA viruses has not been established to date. Here, we investigated if some well characterized DNA viruses belonging to the Poxviridae family are sensitive to human MxA. A cell line inducibly expressing MxA to inhibitory levels showed no anti-Vaccinia virus (VACV) virus activity, indicating either lack of susceptibility of the virus, or the existence of viral factors capable of counteracting MxA inhibition. To determine if VACV resistance to MxA was due to a virus-encoded anti-MxA activity, we performed coinfections of VACV and the MxA-sensitive Vesicular Stomatitis virus (VSV), and show that VACV does not protect VSV from MxA inhibition in trans. Those results were extended to several VACV strains and two CPXV strains, thus confirming that those Orthopoxviruses do not block MxA action. Overall, these results point to a lack of susceptibility of the Poxviridae to MxA antiviral activity.
Cowpox virus
Poxviridae
Orthopoxvirus
Cowpox
DNA virus
Antiviral protein
Cite
Citations (6)
Cowpox
Cowpox virus
Monkeypox
Poxviridae
Orthopoxvirus
Variola virus
Cite
Citations (16)
The EB peptide is a 20-mer that was previously shown to have broad spectrum in vitro activity against several unrelated viruses, including highly pathogenic avian influenza, herpes simplex virus type I, and vaccinia, the prototypic orthopoxvirus. To expand on this work, we evaluated EB for in vitro activity against the zoonotic orthopoxviruses cowpox and monkeypox and for in vivo activity in mice against vaccinia and cowpox. In yield reduction assays, EB had an EC50 of 26.7 μM against cowpox and 4.4 μM against monkeypox. The EC50 for plaque reduction was 26.3 μM against cowpox and 48.6 μM against monkeypox. A scrambled peptide had no inhibitory activity against either virus. EB inhibited cowpox in vitro by disrupting virus entry, as evidenced by a reduction of the release of virus cores into the cytoplasm. Monkeypox was also inhibited in vitro by EB, but at the attachment stage of infection. EB showed protective activity in mice infected intranasally with vaccinia when co-administered with the virus, but had no effect when administered prophylactically one day prior to infection or therapeutically one day post-infection. EB had no in vivo activity against cowpox in mice. While EB did demonstrate some in vivo efficacy against vaccinia in mice, the limited conditions under which it was effective against vaccinia and lack of activity against cowpox suggest EB may be more useful for studying orthopoxvirus entry and attachment in vitro than as a therapeutic against orthopoxviruses in vivo.
Cowpox
Monkeypox
Cowpox virus
Orthopoxvirus
Poxviridae
Cite
Citations (20)
Although a large number of compounds have been identified with antiviral activity against orthopoxviruses in tissue culture systems, it is highly preferred that these compounds have activity in vivo before they can be seriously considered for further development. One of the most commonly used animal models for the confirmation of this activity has been the use of mice infected with either vaccinia or cowpox viruses. These model systems have the advantage that they are relatively inexpensive, readily available and do not require any special containment facilities; therefore, relatively large numbers of compounds can be evaluated in vivo for their activity. The two antiviral agents that have progressed from preclinical studies to human safety trials for the treatment of orthopoxvirus infections are the cidofovir analog, CMX001, and an inhibitor of extracellular virus formation, ST-246. These compounds are the ones most likely to be used in the event of a bioterror attack. The purpose of this communication is to review the advantages and disadvantages of using mice infected with vaccinia and cowpox virus as surrogate models for human orthopoxvirus infections and to summarize the activity of CMX001 and ST-246 in these model infections.
Cowpox virus
Orthopoxvirus
Cowpox
Monkeypox
Poxviridae
Cidofovir
Cite
Citations (24)
Increasing numbers of human cowpox virus infections that are being observed and that particularly affect young non-vaccinated persons have renewed interest in this zoonotic disease. Usually causing a self-limiting local infection, human cowpox can in fact be fatal for immunocompromised individuals. Conventional smallpox vaccination presumably protects an individual from infections with other Orthopoxviruses, including cowpox virus. However, available live vaccines are causing severe adverse reactions especially in individuals with impaired immunity. Because of a decrease in protective immunity against Orthopoxviruses and a coincident increase in the proportion of immunodeficient individuals in today's population, safer vaccines need to be developed. Recombinant subunit vaccines containing cross-reactive antigens are promising candidates, which avoid the application of infectious virus. However, subunit vaccines should contain carefully selected antigens to confer a solid cross-protection against different Orthopoxvirus species. Little is known about the cross-reactivity of antibodies elicited to cowpox virus proteins. Here, we first identified 21 immunogenic proteins of cowpox and vaccinia virus by serological screenings of genomic Orthopoxvirus expression libraries. Screenings were performed using sera from vaccinated humans and animals as well as clinical sera from patients and animals with a naturally acquired cowpox virus infection. We further analyzed the cross-reactivity of the identified immunogenic proteins. Out of 21 identified proteins 16 were found to be cross-reactive between cowpox and vaccinia virus. The presented findings provide important indications for the design of new-generation recombinant subunit vaccines.
Cowpox
Orthopoxvirus
Cowpox virus
Poxviridae
Cite
Citations (11)
Abstract Cowpox with a severe, generalized eruption was diagnosed in an atopic 4-year-old girl by electron microscopy, virus isolation, polymerase chain reaction, and immunoglobulin (Ig) M and low-avidity IgG antibodies. The hemagglutinin gene of the isolate clustered with a Russian cowpox virus strain, and more distantly, with other cowpox and vaccinia virus strains. The patient’s dog had orthopoxvirus-specific antibodies, indicating a possible transmission route.
Cowpox virus
Orthopoxvirus
Cowpox
Poxviridae
Cite
Citations (129)