cowpox virus
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Author(s):  
T. V. Tregubchak ◽  
T. V. Bauer ◽  
R. A. Maksyutov ◽  
E. V. Gavrilova

The eradication of smallpox has become one of the greatest successes of modern health science. This great achievement was made possible thanks to the widespread vaccination of the population. The last case of human infection with smallpox virus occurred in 1977. In 1980, at the 33rd session of the World Health Assembly, routine vaccination against that infection was recommended to be discontinued due to severe post-vaccination complications. However, humanity remains vulnerable to other orthopoxvirus infections closely related to smallpox virus. Recently, the cases of human infection with ortopoxviruses such as monkeypox virus, cowpox virus, vaccinia virus have become more frequent. Also, cases of infection of people with previously unknown orthopoxvirus species are recorded. Zoonotic orthopoxviruses pathogenic for humans, circulating in nature, require a detailed study and monitoring of the emergence of new strains. Their occurrence against the background of the cessation of planned vaccination of the population against smallpox virus can lead to the emergence of new highly pathogenic viruses. This review contains information on cases of human infection with orthopoxviruses around the world for the period 2008–2018. It also describes epidemiological anamnesis and the relations between cases of human infection in different countries due to the spread of viruses over a wide area, the movement of people between countries, population contacts with domestic and wild animals. Also, this paper provides information on the infection of people with previously unknown strains of orthopoxviruses.


Author(s):  
S. Shchelkunov ◽  
A. Sergeev ◽  
S. Yakubitskyi ◽  
K. Titova ◽  
S. Pyankov

Smallpox eradication and absence of adequate animal model of smallpox infection causes necessity of the assessment of immunogenic and protective properties of the created by genetic engineering approaches live attenuated smallpox vaccines in several animal models of orthopoxviral infections. In this research comparison of the immunogenic and protective properties of the recombinant vaccinia virus (VACV) LIVP-GFP after intradermal (i/d) injection to mice, guinea pigs and rabbits were carried out. Doses of LIVP-GFP immunization in all animal species were 2x104 or 2x106 pfu. Control animals were injected with saline. Blood sampling was done on 28 day after virus LIVP-GFP or saline injection. Blood samples were taken intravitally from the retro-orbital venous sinus of mice, from heart of guinea pigs or marginal ear vein of rabbits. Serum was isolated from blood samples by precipitating blood cells via centrifugation. The anti-VACV IgG titers in the serum samples were determined by ELISA. On 30 day of the experiment immunized by virus LIVP-GFP or control animals were intranasal infected with lethal doses of the corresponding orthopoxviruses to which every animal species was sensitive. Mice were infected by cowpox virus (CPXV) strain GRI-90 in dose 68 LD50, guinea pigs - by VACV GPA in dose 56 LD50, rabbits – by VACV HB-92 in dose 100 LD50. All control animals after that were died, but all animals immunized by attenuated recombinant virus LIVP-GFP in dose 2x106 pfu were survived. In case of the LIVP-GFP immunization dose 2x104 pfu 88% of mice were survived after CPXV infection, 67% of rabbits were survived after VACV HB-92 infection, and 50% of guinea pigs were survived after VACV GPA infection. ELISA data of the blood serums had shown correlation of the levels of VACV-specific antibodies with levels of protection in the corresponding animals. On the basis of the obtained data it could be concluded that all three studied models animal-orthopoxvirus allow give an adequate evaluation of immunogenicity and protectiveness of the created modern attenuated vaccines against smallpox and other orthopoxviral human infections. BALB/c mice are the most convenient subject of this investigation


2021 ◽  
Vol 27 (10) ◽  
pp. 2570-2577
Author(s):  
Audrey Ferrier ◽  
Gaelle Frenois-Veyrat ◽  
Evelyne Schvoerer ◽  
Sandrine Henard ◽  
Fanny Jarjaval ◽  
...  

2021 ◽  
Vol 11 (9) ◽  
pp. 43-48
Author(s):  
Konrad Kania ◽  
Maria Kalicka ◽  
Tomasz Korzec ◽  
Przemyslaw Raczkiewicz ◽  
Monika Kuc

Background:Despite the elimination of smallpox, other orthopoxviruses, including cowpox virus, still infect humans. Wild rodents are its natural reservoir. Infections in humans are commonly reported from contact with sick domestic cats, rarely directly from rats. Cow pox in humans is a rare zoonotic disease, the diagnosis of which is problematic due to its rarity and thus the lack of clinical experience.Case report:Presented with a summary of the available clinical data on a 15-year-old boy who became infected with cowpox by a domestic cat.The patient developed cutaneous macular changes in the facial area. Within 3 weeks of the onset of symptoms, the lesions progressed through the papular, vesicular and pustular stages before forming a hard black eschars (2 cm in diameter) with erythema and edema and regional lifadenopathy. Differential diagnosis consisting of cat scratch disease, anthrax and brucellosis excluded microbiological examination. The lesions left scars after 8 weeks of continuous topical antiseptic treatment.Conclusions:The clinical course may be complicated, and the improvement takes 4 to 8 weeks. Infection which entered through the skin changes was the cause of antibiotic therapy. Cowpox should be suspected in patients with poorly healing skin lesions accompanied by a painful black eschars with erythema and local lymphadenopathy.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Daniel Bourquain ◽  
Livia Schrick ◽  
Bernd Karsten Tischer ◽  
Klaus Osterrieder ◽  
Lars Schaade ◽  
...  

AbstractZoonotic orthopoxvirus infections continue to represent a threat to human health. The disease caused by distinct orthopoxviruses differs in terms of symptoms and severity, which may be explained by the unique repertoire of virus factors that modulate the host’s immune response and cellular machinery. We report here on the construction of recombinant cowpox viruses (CPXV) which either lack the host range factor p28 completely or express truncated variants of p28. We show that p28 is essential for CPXV replication in macrophages of human or mouse origin and that the C-terminal RING finger domain of p28 is necessary to allow CPXV replication in macrophages.


Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1631
Author(s):  
Sergei N. Shchelkunov ◽  
Alexander A. Sergeev ◽  
Stanislav N. Yakubitskiy ◽  
Ksenia A. Titova ◽  
Stepan A. Pyankov ◽  
...  

Mass vaccination has played a critical role in the global eradication of smallpox. Various vaccinia virus (VACV) strains, whose origin has not been clearly documented in most cases, have been used as live vaccines in different countries. These VACV strains differed in pathogenicity towards various laboratory animals and in reactogenicity exhibited upon vaccination of humans. In this work, we studied the development of humoral and cellular immune responses in BALB/c mice inoculated intranasally (i.n.) or intradermally (i.d.) with the VACV LIVP strain at a dose of 105 PFU/mouse, which was used in Russia as the first generation smallpox vaccine. Active synthesis of VACV-specific IgM in the mice occurred on day 7 after inoculation, reached a maximum on day 14, and decreased by day 29. Synthesis of virus-specific IgG was detected only from day 14, and the level increased significantly by day 29 after infection of the mice. Immunization (i.n.) resulted in significantly higher production of VACV-specific antibodies compared to that upon i.d. inoculation of LIVP. There were no significant differences in the levels of the T cell response in mice after i.n. or i.d. VACV administration at any time point. The maximum level of VACV-specific T-cells was detected on day 14. By day 29 of the experiment, the level of VACV-specific T-lymphocytes in the spleen of mice significantly decreased for both immunization procedures. On day 30 after immunization with LIVP, mice were infected with the cowpox virus at a dose of 46 LD50. The i.n. immunized mice were resistant to this infection, while 33% of i.d. immunized mice died. Our findings indicate that the level of the humoral immune response to vaccination may play a decisive role in protection of animals from orthopoxvirus reinfection.


Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1571
Author(s):  
Reed F. Johnson ◽  
Lauren A. Keith ◽  
Timothy K. Cooper ◽  
Srikanth Yellayi ◽  
Nicole M. Josleyn ◽  
...  

Hemorrhagic smallpox, caused by variola virus (VARV), was a rare but nearly 100% lethal human disease manifestation. Hemorrhagic smallpox is frequently characterized by secondary bacterial infection, coagulopathy, and myocardial and subendocardial hemorrhages. Previous experiments have demonstrated that intravenous (IV) cowpox virus (CPXV) exposure of macaques mimics human hemorrhagic smallpox. The goal of this experiment was to further understand the onset, nature, and severity of cardiac pathology and how it may contribute to disease. The findings support an acute late-stage myocarditis with lymphohistiocytic infiltrates in the CPXV model of hemorrhagic smallpox.


Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 663
Author(s):  
Kirk Osmond Douglas ◽  
Claire Cayol ◽  
Kristian Michael Forbes ◽  
Thelma Alafia Samuels ◽  
Olli Vapalahti ◽  
...  

Background: Rodents are reservoirs for several zoonotic pathogens that can cause human infectious diseases, including orthohantaviruses, mammarenaviruses and orthopoxviruses. Evidence exists for these viruses circulating among rodents and causing human infections in the Americas, but much less evidence exists for their presence in wild rodents in the Caribbean. Methods: Here, we conducted serological and molecular investigations of wild rodents in Barbados to determine the prevalence of orthohantavirus, mammarenavirus and orthopoxvirus infections, and the possible role of these rodent species as reservoirs of zoonotic pathogens. Using immunofluorescent assays (IFA), rodent sera were screened for the presence of antibodies to orthohantavirus, mammarenavirus (Lymphocytic choriomeningitis virus—LCMV) and orthopoxvirus (Cowpox virus—CPXV) infections. RT-PCR was then conducted on orthohantavirus and mammarenavirus-seropositive rodent sera and tissues, to detect the presence of viral RNA. Results: We identified antibodies against orthohantavirus, mammarenavirus, and orthopoxvirus among wild mice and rats (3.8%, 2.5% and 7.5% seropositivity rates respectively) in Barbados. No orthohantavirus or mammarenavirus viral RNA was detected from seropositive rodent sera or tissues using RT–PCR. Conclusions: Key findings of this study are the first serological evidence of orthohantavirus infections in Mus musculus and the first serological evidence of mammarenavirus and orthopoxvirus infections in Rattus norvegicus and M. musculus in the English-speaking Caribbean. Rodents may present a potential zoonotic and biosecurity risk for transmission of three human pathogens, namely orthohantaviruses, mammarenaviruses and orthopoxviruses in Barbados.


Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 406
Author(s):  
Iago José da Silva Domingos ◽  
Jaqueline Silva de Oliveira ◽  
Kamila Lorene Soares Rocha ◽  
Danilo Bretas de Oliveira ◽  
Erna Geessien Kroon ◽  
...  

Orthopoxvirus (OPV) infections have been present in human life for hundreds of years. It is known that Variola virus (VARV) killed over 300 million people in the past; however, it had an end thanks to the physician Edward Jenner (who developed the first vaccine in history) and also thanks to a massive vaccination program in the 20th century all over the world. Although the first vaccine was created using the Cowpox virus (CPXV), it turned out later that the Vaccinia virus was the one used during the vaccination program. VACV is the etiological agent of bovine vaccinia (BV), a zoonotic disease that has emerged in Brazil and South America in the last 20 years. BV has a great impact on local dairy economies and is also a burden to public health. In this review, we described the main events related to VACV and BV emergence in Brazil and South America, the increase of related scientific studies, and the issues that science, human and animal medicine are going to face if we do not be on guard to this virus and its disease.


2021 ◽  
Author(s):  
Leon C.W. Lin ◽  
Sarah N. Croft ◽  
Nathan P. Croft ◽  
Yik Chun Wong ◽  
Stewart A. Smith ◽  
...  

Vaccinia virus (VACV) was the vaccine used to eradicate smallpox and is being repurposed as a vaccine vector. CD8+ T cells are key anti-viral mediators, but require priming to become effector or memory cells. Priming requires an interaction with dendritic cells that are either infected (direct priming), or that have acquired virus proteins but remain uninfected (cross priming). To investigate CD8+ T cell priming pathways for VACV, we engineered the virus to express CPXV12 and CPXV203, two inhibitors of antigen presentation encoded by cowpox virus. These intracellular proteins would be expected to block direct but not cross priming. The inhibitors had diverse impacts on the size of anti-VACV CD8+ T cell responses across epitopes and by different infection routes in mice, superficially suggesting variable use of direct and cross priming. However, when we then tested a form of antigen that requires direct priming, we found surprisingly that CD8+ T cell responses were not diminished by co-expression with CPXV12 and CPXV203. We then directly quantified the impact of CPXV12 and CPXV203 on viral antigen presentation using mass spectrometry, which revealed strong, but incomplete inhibition of antigen presentation by the CPXV proteins. Therefore, direct priming of CD8+ T cells by poxviruses is robust enough to withstand highly potent viral inhibitors of antigen presentation. This is a reminder of the limits of viral immune evasion and shows that viral inhibitors of antigen presentation cannot be assumed to dissect cleanly direct and cross priming of anti-viral CD8+ T cells. Importance CD8+ T cells are key to anti-viral immunity, so it is important to understand how they are activated. Many viruses have proteins that protect infected cells from T cell attack by interfering with the process that allows virus infection to be recognised by CD8+ T cells. It is thought that these proteins would also stop infected cells from activating T cells in the first place. However, we show here that this is not the case for two very powerful inhibitory proteins from cowpox virus. This demonstrates the flexibility and robustness of immune processes that turn on the immune responses required to fight infection.


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