ABSTRACT
Intratracheal (i.t.) infection of mice with cowpox virus (CPXV), is lethal at a lower dose than intranasal (i.n.) inoculation. CPXV deleted for cytokine response modifier A (CPXVDeltacrmA) was attenuated compared to CPXV after i.t. inoculation. This attenuation could not be attributed to differences in virus replication, immunomodulators, or cells infiltrating the lungs. Deletion of crmA also caused attenuation during intradermal (i.d.) infection. In contrast to i.t.-inoculated virus, deletion of crmA reduced virus replication at the site of infection. This difference correlated to increased numbers of CD3(+) cells in CPXVDeltacrmA-associated dermal lesions. Thus, crmA is a virulence factor in mice during either pulmonary or dermal cowpox infection; however the influence of crmA is more evident during i.d. inoculation. This suggests that the host immune response differs in the two routes of infection and emphasizes the need to consider the effect of route of infection when examining functions of virulence factors in vivo.
Subject(s)
Cowpox virus/genetics , Cowpox/veterinary , Serpins/genetics , Viral Proteins/genetics , Animals , Caspases/metabolism , Cowpox/enzymology , Cowpox/mortality , Cowpox/physiopathology , Cowpox virus/pathogenicity , Gene Expression Regulation, Viral , Humans , Mice , Mice, Inbred C57BL , Smallpox/virology , Species Specificity , VirulenceABSTRACT
An anti-poxvirus vaccine based on replicon particles of Venezuelan equine encephalitis virus (VRP) is being developed. The cowpox virus genes encoding structural proteins corresponding to vaccinia virus proteins A33, B5, and A27 were each expressed from VRP. High serum IgG titers against these proteins were generated in BALB/c mice vaccinated with each of these VRP. VRP induced both IgG1 and IgG2a with a strong predominance of IgG2a production. The response is long-lasting, as evidenced by the retention of high anti-B5 serum IgG titers through at least 50 weeks after priming immunization. Mice vaccinated with B5-, A33- or A27-VRP individually or together survived intranasal challenge with cowpox virus, with the multivalent vaccine formulation providing more effective protection from weight loss and clinical signs of illness than the monovalent vaccines. These results demonstrate that VRP may provide an effective alternative to vaccinia virus vaccines against poxvirus infection.
Subject(s)
Cowpox virus/immunology , Cowpox/prevention & control , Encephalitis Virus, Venezuelan Equine/genetics , Vaccines, Synthetic/immunology , Viral Structural Proteins/immunology , Viral Vaccines/immunology , Amino Acid Sequence , Animals , Antibodies, Viral/blood , Body Weight , Cowpox/immunology , Cowpox/physiopathology , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Female , Genetic Vectors/genetics , Immunoglobulin G/blood , Immunologic Memory , Mice , Mice, Inbred BALB C , Molecular Sequence Data , Replicon/genetics , Sequence Homology, Amino Acid , Survival Analysis , Time Factors , Vaccines, Synthetic/genetics , Viral Structural Proteins/genetics , Viral Vaccines/geneticsABSTRACT
The specific features of reproduction of EP-2 strain of cowpox virus (CPV) were studied in intranasally infected BALC/C mice by light and electron microscopy. Virus replication was found in the ciliated, intercalary, basal, and goblet cells (the nasal respiratory area), basal and supporting cells (the nasal olfactory area), ciliated, intercalary, goblet cells (the tracheal and bronchial epithelium), and collagen-producing, Schwann's, endothelial, smooth muscle, and adventitial cells. It has been shown that the CPV strain EP-2 locally replicates in the nasal cavity, trachea, and large bronchi and that there is no generalized infection.
Subject(s)
Cowpox virus/physiology , Cowpox/physiopathology , Respiratory System/virology , Virus Replication/physiology , Animals , Cattle , Cowpox/pathology , Cowpox virus/isolation & purification , Elephants/virology , Mice , Mice, Inbred BALB C , Respiratory System/pathologyABSTRACT
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. In Finnish wild rodents, orthopoxvirus seroprevalences were 0%-92%, in humans the seroprevalence was 100% in the age group >50, decreasing towards younger age groups.
Subject(s)
Antibodies, Viral/isolation & purification , Cowpox/physiopathology , Animals , Child, Preschool , Cowpox/diagnosis , Cowpox virus/immunology , Cowpox virus/isolation & purification , Female , Finland , HumansABSTRACT
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.
