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Comparison of cowpox-like viruses isolated from European zoos. Brief report.

Poxviruses isolated from captive carnivores in Russia (Moscow virus) and elephants in Germany (elephant virus) were very closely-related to cowpox virus. Immunological analysis with absorbed sera separated elephant virus but not cowpox and Moscow virus, whereas polypeptide analysis separated cowpox but not elephant and Moscow virus. A combination of biological tests separated all three. The epidemiological implications are briefly reviewed.

Animals↗

Serologically cross-reactive polypeptides in vaccinia, cowpox and Shope fibroma viruses.

An immunoprecipitation method coupled with SDS-polyacrylamide gel electrophoresis (SDS-PAGE) was used to identify the serologically cross-reactive polypeptides in Orthopoxvirus (vaccinia and cowpox viruses) and Leporipoxvirus (Shope fibroma virus). Two early and four late polypeptides in cells infected with vaccinia or cowpox virus were specifically immunoprecipitated with antiserum against Shope fibroma virus. Two early and two late polypeptides in cells infected with Shope fibroma virus cross-reacted with both antiserum against vaccinia virus and antiserum against cowpox virus. The possibility of the common polypeptides being related to nucleoprotein antigen in these cross-reactive polypeptides was discussed.

Antigens, Viral↗

Comparative studies on LS antigens induced by vaccinia and cowpox viruses.

The constituents of LS antigen from cells infected with vaccinia virus and with cowpox virus were compared by immunoprecipitation and SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Antiserum to the LS antigen from cells infected with vaccinia virus reacted with at least five polypeptides in cells infected with either virus. Four of these polypeptides were similar sizes in cells infected with the two viruses. However, one major polypeptide with a mol. wt. of about 100 000 (100 K) detected in cells infected with vaccinia virus was not found in cells infected with cowpox virus. Conversely, a polypeptide with a mol. wt. of about 60 000 (60K) was detected only in cells infected with cowpox virus.

Animals↗

Isolation of cowpox virus clones deficient in production of type A inclusions: relationship to the production of diffusible LS antigen.

Cowpox virus clones (A- clones) deficient in production of type A inclusions were isolated from two cowpox strains, Amsterdam and 53. These clones did not differ from their parents in major markers such as pock morphology in chorioallantoic membranes and pathogenicity in the rabbit skin. However, the LS antigens induced by A- clones developed precipitin lines in agar gel diffusion tests, while the antigens from their parents failed to precipitate. Immunofluorescence and agar gel diffusion tests revealed that antigens detectable by antisera against purified type A inclusions and LS antigens were closely related to each other. These findings suggest that the A- clones might be variants of cowpox virus which have lost the ability to assemble LS antigens into type A inclusions.

Animals↗

Three cases of cowpox infection of domestic cats.

Since October 1982 three cases of cowpox infection of the cat have been presented at a veterinary practice. The disease began as a focal dermatitis on the face or paws which spread after several days to the rest of the body. Two weeks after appearing the pocks scabbed over and fell off leaving hairless skin. There were few systemic signs and therapy did not appear to influence the course of the disease. Diagnosis was confirmed by the demonstration of pox virions or inclusion bodies in skin biopsy or scab material using electron microscopy and by isolation of cowpox virus in chick embryos. High antibody titres to cowpox were observed in the sera of two cats.

Animals↗

Studies on the polypeptides of poxvirus. I. Comparison of structural polypeptides in vaccina, cowpox and Shope fibroma viruses.

Radioactively labeled vaccinia, cowpox and Shope fibroma virions free from any detectable contamination with host cell protein, were dissociated into their constituent polypeptides, and these were then analyzed by SDS-polyacrylamide gel electrophoresis and autoradiography. The profiles of constituent polypeptide bands of four strains of vaccinia virus (IHD-W, IHD-J, Lister and DIs) were almost the same, except that a polypeptide of about 41,000 daltons was not detectable in the autoradiogram of strain IHD-W which has no hemagglutinin. The profile of polypeptide bands of cowpox virions was also almost the same as that of vaccinia virions, except for several polypeptides of about 40,000 to 50,000 daltons, but the profile of Shope fibroma virions differed considerably from that of vaccinia or cowpox virions.

Electrophoresis, Polyacrylamide Gel↗

[Laboratory-confirmed case of human infection with ratpox (cowpox)].

The present work describes a case of human disease resulting from the bite of a white rat and caused by a biological variant of cowpox virus. The isolates obtained from the sick man and the white rats which had been the source of this infection proved to be identical and did not differ from the biological variants of cowpox virus, isolated earlier from white rats and carnivorous animals of the family Felidae. Thus, the possibility of ratpox (cowpox) transmission from sick rodents to man was established.

Adult↗

New outlook on the biology of cowpox virus.

Analysis of cowpox outbreaks revealed an extremely wide range of virus pathogenicity including 9 orders of mammals. Recent serological and virological data support the hypothesis that wild rodents may be a natural reservoir of cowpox virus. Cowpox infection of humans occurring without any contact with infected cattle (registered in the U. K. and Poland) is especially interesting for medical and veterinary virology. Surveillance seems justified of the possible virus dissemination beyond its natural reservoir resulting in further infection of man and animals.

Animals↗

Severe and prolonged inflammatory response to localized cowpox virus infection in footpads of C5-deficient mice: investigation of the role of host complement in poxvirus pathogenesis.

Poxviruses are a large, complex group of highly successful pathogens that cause disease in humans and other animals. They encode several proteins postulated to be involved in the evasion of host immunity and therefore serve as excellent models for understanding virus-host interaction during the early stages of viral infection. Vaccinia virus, the best characterized member of the poxviridae family, encodes a 35-kDa major secretory polypeptide termed vaccinia virus complement control protein (VCP), which is structurally related to the family of human and mouse complement control proteins. Members of the family of complement control proteins have been shown to inhibit complement-mediated opsonization of bacteria and induction of inflammatory and phagocytic responses in vitro. Insertional inactivation of the VCP gene results in attenuation of viral virulence in vivo. The role of host complement in the inflammatory response to poxvirus infection has not been systematically investigated. Prior to determining the role of VCP on inflammatory responses in vivo, we decided to investigate the role of host complement in the progression of viral infection. We have compared the effects of injection of cowpox virus, primarily a rodent virus, into footpads of congenic mice strains B10.D2/nSnJ (C5-sufficient) and B10.D2/oSnJ (C5-deficient). The effects of the injection were monitored macroscopically by measuring the specific swelling response immediately following primary injection and subsequently after reinfection and by histological examination of the stained sections of the footpads. Our results indicate that there is a significant variation in the primary response in the two different mouse strains to cowpox virus infection. The specific swelling response observed in measurements from the footpads of the B10.D2/oSnJ mice was significantly greater, persisted for a longer duration, and was accompanied by severe ulceration, edema, induration, and hemorrhaging. Reinjection of the footpads after a 3-month period, during which time the swelling had subsided and the footpad had fully recovered to its original size and appearance, showed no significant differences between the two strains. This strongly suggests that the host complement plays a significant role during the initial response to poxvirus infection.

Animals↗

Cowpox virus contains two copies of an early gene encoding a soluble secreted form of the type II TNF receptor.

The inverted terminal repeats of the DNA of cowpox virus (Brighton Red strain) contain the crmB gene, an additional member of a family of viral genes that modify cytokine responses to infection. The crmB gene is transcribed from an early promoter. The primary product is a 355-amino-acid protein containing a signal peptide sequence and three potential N-linked glycosylation sites. The mature gene product is a secreted soluble protein that has an apparent molecular mass of 48 kDa. TNF alpha and TNF beta bind to this protein in a competitive manner, consistent with the sequence of its N-terminal 176 amino acids, which closely resembles the ligand-binding domains of the type II (75-kDa) human TNF receptor. The sequence of the C-terminal 161 amino acids of the CrmB protein is unlike that of human TNF receptors, but overall, the CrmB protein is similar to the T2 proteins of the leporipoxviruses (48% identity) and the predicted product of the G4R/G2R open reading frame of variola virus (85% identity), suggesting that not only the TNF-binding domains but also the C-terminal regions contribute to the functions of these viral proteins. These results show that orthopoxiviruses such as cowpox virus encode secreted forms of TNF receptors that can contribute to the modification of TNF-mediated antiviral processes.

Amino Acid Sequence↗

[Cowpox virus infection in a child].

UNLABELLED: Although human cowpox virus infection is rare nowadays, an animal reservoir of this virus still exists. The general course of cowpox virus infections is usually benign but the diagnosis is difficult and often late. CASE REPORT: An 11-year-old boy, owner of two cats, presented with an infected sacral wound lesion associated with fever and lymph nodes. The wound became necrotic and other cutaneous and mucous membrane lesions developed secondarily. Blood tests did not show hyperleukocytosis or a systemic inflammatory response. Concurrently one of the cats was examined by a veterinary because of multifocal cutaneous lesions. Evocative skin biopsy specimens from the animal and, secondarily from the patient, allowed the identification of orthopoxvirus. Evolution was slowly favourable under symptomatic treatment. CONCLUSION: Poxviruses are responsible for many animal and human diseases, the most famous of them being smallpox which today is considered eradicated. Vaccination against smallpox is no longer performed since 1977. Whether the arrest of vaccinations against smallpox may induce the apparition of other poxviruses infections or alter their clinical expression is an open question.

Animals↗

Cowpox virus infection associated with a streptococcal septicaemia in a foal.

Cowpox virus infection associated with a streptococcal septicaemia was diagnosed in a weak German Warmblood filly, born 29 days prematurely, and humanely destroyed on the sixth day of life. At necropsy, ulcerative lesions in the alimentary tract, colitis, polyarthritis and nephritis were observed. Transmission electron microscopical examination of specimens from ulcerative lesions revealed typical orthopox virions. Cowpox virus was unequivocally identified by virological and molecular-biological methods.

Animals↗

Treatment of aerosolized cowpox virus infection in mice with aerosolized cidofovir.

The Brighton strain of cowpox virus causes lethal bronchopneumonia when delivered as a small-particle (1 microm) aerosol to weanling BALB/c mice. We showed previously that this disease can be prevented or cured with one subcutaneous injection of cidofovir (HPMPC, Vistide). To determine whether even better results could be obtained by delivering the drug directly to the respiratory tract, we administered cidofovir by small-particle aqueous aerosol before or after aerosolized cowpox infection. In a series of five experiments, aerosol doses of 0.5-5 mg/kg were always more effective than 25 mg/kg and sometimes more effective than 100 mg/kg injected subcutaneously, as measured by changes in body and lung weight, lung viral titers, pulmonary pathology and survival. A cyclic analog ((1-[(S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl] cytosine) (cHPMPC) was less protective. The results suggest that aerosolized cidofovir would be effective for prophylaxis or early post-exposure therapy of human smallpox or monkeypox virus infection.

Administration, Inhalation↗

Cowpox virus infection in an 11-year-old girl.

We describe an 11-year-old girl with a cowpox virus infection, who presented with a 14-day-old crusted, ulcerated nodule on the chin/neck and a 6-day-old eroded blister on the left leg. The girl lived in a rural environment, had close contact to several cats from the neighborhood, and had an atopic predisposition. The presence of orthopox virus in the lesion on the left leg was demonstrated by electron microscopy (negative staining, transmission electron microscopy) and virus isolation. Classification as a cowpox virus was determined by polymerase chain reaction (PCR), followed by restriction enzyme digestion of the PCR product.

Animals↗

Cowpox infection of the nose.

A case of cowpox infection presenting as a necrotising cellulitis of the nasal tip and vestibule is reported. Diagnosis was established by identification of the pox virus particles from tissue culture of the nasal biopsy using electronic microscopy and the characteristic lesions on chorio-allantoic membrane produced by the virus. Cowpox of the external nose and transmission of the infection from a dog have not to our knowledge been reported previously.

Adult↗

Cowpox: reservoir hosts and geographic range.

It is generally accepted that the reservoir hosts of cowpox virus are wild rodents, although direct evidence for this is lacking for much of the virus's geographic range. Here, through a combination of serology and PCR, we demonstrate conclusively that the main hosts in Great Britain are bank voles, wood mice and short-tailed field voles. However, we also suggest that wood mice may not be able to maintain infection alone, explaining the absence of cowpox from Ireland where voles are generally not found. Infection in wild rodents varies seasonally, and this variation probably underlies the marked seasonal incidence of infection in accidental hosts such as humans and domestic cats.

Animals↗

Anti-cowpox virus activities of certain adenosine analogs, arabinofuranosyl nucleosides, and 2'-fluoro-arabinofuranosyl nucleosides.

Nucleoside analogs were investigated for their potential to inhibit cowpox virus (a surrogate for variola and monkeypox viruses) in cell culture and in lethal respiratory infections in mice. Cell culture antiviral activity was determined by plaque reduction assays, with cytotoxicity determined by cell proliferation assays. Selectivity indices (SI's, 50% cytotoxic concentration divided by 50% virus-inhibitory concentration) were determined for 15 compounds. Three arabinofuranosyl (Ara) nucleosides showed activity in mouse mammary tumor (C127I) cells: guanine (Ara-G), thymine (Ara-T), and adenine (Ara-A) with SI's of 113, 61, and 95, respectively. The 2'-fluoro-Ara nucleosides of 5-F-cytosine (FIAC), 5-methyluracil (FMAU), and 5-iodouracil (FIAU) exhibited SI's of 148, 77, and 29, respectively. Other potent compounds included cidofovir (a positive control) and 3'-O-methyladenosine, with SI values of 164 and 56, respectively. In general, assays performed in African green monkey kidney (Vero) cells produced lower SI's than in C127I cells, except for 5-iodo-2'-deoxyuridine (IDU) which had an SI of > 71 in Vero cells and 3.1 in C127I cells. Intranasal infection of mice with cowpox virus was followed a day later by twice daily intraperitoneal treatment with compounds for 5 days. Ara-A was active at 300 mg/kg/day (40% survival), FMAU at 100 mg/kg/day (70% survival), and cidofovir (given for 1 day only) at 100 mg/kg (80-100% survival). None of the other compounds, including IDU, prevented death nor delayed the time to death. Cidofovir had the best potential for treating orthopoxvirus infections of those tested.

Adenosine↗