Experimental studies on transformation of the variola virus into the vaccinia virus

1963 ◽  
Vol 12 (5) ◽  
pp. 579-599 ◽  
Author(s):  
A. Herrlich ◽  
A. Mayr ◽  
H. Mahnel ◽  
E. Munz
Keyword(s):  
Vaccinia Virus ◽  
Experimental Studies ◽  
Variola Virus

scholarly journals Immunological Memory after Exposure to Variola Virus, Monkeypox Virus, and Vaccinia Virus

2007 ◽  
Vol 195 (8) ◽  
pp. 1151-1159 ◽  
Author(s):  
Sumathi Sivapalasingam ◽  
Jeffrey S. Kennedy ◽  
William Borkowsky ◽  
Fred Valentine ◽  
Ming‐Xia Zhan ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Immunological Memory ◽  
Variola Virus ◽  
Monkeypox Virus

scholarly journals Characterization of Chimpanzee/Human Monoclonal Antibodies to Vaccinia Virus A33 Glycoprotein and Its Variola Virus Homolog In Vitro and in a Vaccinia Virus Mouse Protection Model

2007 ◽  
Vol 81 (17) ◽  
pp. 8989-8995 ◽  
Author(s):  
Zhaochun Chen ◽  
Patricia Earl ◽  
Jeffrey Americo ◽  
Inger Damon ◽  
Scott K. Smith ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Vaccinia Virus ◽  
Protective Efficacy ◽  
Variola Virus ◽  
Binding Affinities ◽  
Amino Acid Residues ◽  
C Terminus ◽  
20 Nm

ABSTRACT Three distinct chimpanzee Fabs against the A33 envelope glycoprotein of vaccinia virus were isolated and converted into complete monoclonal antibodies (MAbs) with human γ1 heavy-chain constant regions. The three MAbs (6C, 12C, and 12F) displayed high binding affinities to A33 (Kd of 0.14 nM to 20 nM) and may recognize the same epitope, which was determined to be conformational and located within amino acid residues 99 to 185 at the C terminus of A33. One or more of the MAbs were shown to reduce the spread of vaccinia virus as well as variola virus (the causative agent of smallpox) in vitro and to more effectively protect mice when administered before or 2 days after intranasal challenge with virulent vaccinia virus than a previously isolated mouse anti-A33 MAb (1G10) or vaccinia virus immunoglobulin. The protective efficacy afforded by anti-A33 MAb was comparable to that of a previously isolated chimpanzee/human anti-B5 MAb. The combination of anti-A33 MAb and anti-B5 MAb did not synergize the protective efficacy. These chimpanzee/human anti-A33 MAbs may be useful in the prevention and treatment of vaccinia virus-induced complications of vaccination against smallpox and may also be effective in the immunoprophylaxis and immunotherapy of smallpox and other orthopoxvirus diseases.

scholarly journals Ancient Gene Capture and Recent Gene Loss Shape the Evolution of Orthopoxvirus-Host Interaction Genes

mBio ◽  
2021 ◽  
Author(s):  
Tatiana G. Senkevich ◽  
Natalya Yutin ◽  
Yuri I. Wolf ◽  
Eugene V. Koonin ◽  
Bernard Moss
Keyword(s):  
Immune Response ◽  
Vaccinia Virus ◽  
Gene Loss ◽  
Genome Replication ◽  
Variola Virus ◽  
Human Pathogens ◽  
Gene Capture ◽  
Host Interaction ◽  
Virion Morphogenesis ◽  
Ancient Gene

Orthopoxviruses (ORPV) include smallpox (variola) virus, one of the most devastating human pathogens, and vaccinia virus, comprising the vaccine used for smallpox eradication. Among roughly 200 ORPV genes, about half are essential for genome replication and expression as well as virion morphogenesis, whereas the remaining half consists of accessory genes counteracting the host immune response.

scholarly journals Variola virus F1L is a Bcl-2-like protein that unlike its vaccinia virus counterpart inhibits apoptosis independent of Bim

2015 ◽  
Vol 6 (3) ◽  
pp. e1680-e1680 ◽  
Author(s):  
B Marshall ◽  
H Puthalakath ◽  
S Caria ◽  
S Chugh ◽  
M Doerflinger ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Variola Virus

scholarly journals Species Specificity of Vaccinia Virus Complement Control Protein for the Bovine Classical Pathway Is Governed Primarily by Direct Interaction of Its Acidic Residues with Factor I

2017 ◽  
Vol 91 (19) ◽  
Author(s):  
Jitendra Kumar ◽  
Viveka Nand Yadav ◽  
Swastik Phulera ◽  
Ashish Kamble ◽  
Avneesh Kumar Gautam ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Classical Pathway ◽  
Variola Virus ◽  
Complement Control Protein ◽  
Factor I ◽  
Functional Assays ◽  
Alternative Complement ◽  
Cofactor Activity ◽  
Complement Regulator ◽  
Control Protein

ABSTRACTPoxviruses display species tropism—variola virus is a human-specific virus, while vaccinia virus causes repeated outbreaks in dairy cattle. Consistent with this, variola virus complement regulator SPICE (smallpox inhibitor of complement enzymes) exhibits selectivity in inhibiting the human alternative complement pathway and vaccinia virus complement regulator VCP (vaccinia virus complement control protein) displays selectivity in inhibiting the bovine alternative complement pathway. In the present study, we examined the species specificity of VCP and SPICE for the classical pathway (CP). We observed that VCP is ∼43-fold superior to SPICE in inhibiting bovine CP. Further, functional assays revealed that increased inhibitory activity of VCP for bovine CP is solely due to its enhanced cofactor activity, with no effect on decay of bovine CP C3-convertase. To probe the structural basis of this specificity, we utilized single- and multi-amino-acid substitution mutants wherein 1 or more of the 11 variant VCP residues were substituted in the SPICE template. Examination of these mutants for their ability to inhibit bovine CP revealed that E108, E120, and E144 are primarily responsible for imparting the specificity and contribute to the enhanced cofactor activity of VCP. Binding and functional assays suggested that these residues interact with bovine factor I but not with bovine C4(H2O) (a moiety conformationally similar to C4b). Mapping of these residues onto the modeled structure of bovine C4b-VCP-bovine factor I supported the mutagenesis data. Taken together, our data help explain why the vaccine strain of vaccinia virus was able to gain a foothold in domesticated animals.IMPORTANCEVaccinia virus was used for smallpox vaccination. The vaccine-derived virus is now circulating and causing outbreaks in dairy cattle in India and Brazil. However, the reason for this tropism is unknown. It is well recognized that the virus is susceptible to neutralization by the complement classical pathway (CP). Because the virus encodes a soluble complement regulator, VCP, we examined whether this protein displays selectivity in targeting bovine CP. Our data show that it does exhibit selectivity in inhibiting the bovine CP and that this is primarily determined by its amino acids E108, E120, and E144, which interact with bovine serine protease factor I to inactivate bovine C4b—one of the two subunits of CP C3-convertase. Of note, the variola complement regulator SPICE contains positively charged residues at these positions. Thus, these variant residues in VCP help enhance its potency against the bovine CP and thereby the fitness of the virus in cattle.

scholarly journals Low-Resolution Structure of Vaccinia Virus DNA Replication Machinery

2012 ◽  
Vol 87 (3) ◽  
pp. 1679-1689 ◽  
Author(s):  
Céleste Sèle ◽  
Frank Gabel ◽  
Irina Gutsche ◽  
Ivan Ivanov ◽  
Wim P. Burmeister ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Recombinant Expression ◽  
Rotational Symmetry ◽  
Vaccination Campaign ◽  
Virus Genome ◽  
Genome Replication ◽  
Variola Virus ◽  
Replication Machinery ◽  
Content Type ◽  
Rolling Circle

ABSTRACTSmallpox caused by the poxvirus variola virus is a highly lethal disease that marked human history and was eradicated in 1979 thanks to a worldwide mass vaccination campaign. This virus remains a significant threat for public health due to its potential use as a bioterrorism agent and requires further development of antiviral drugs. The viral genome replication machinery appears to be an ideal target, although very little is known about its structure. Vaccinia virus is the prototypic virus of theOrthopoxvirusgenus and shares more than 97% amino acid sequence identity with variola virus. Here we studied four essential viral proteins of the replication machinery: the DNA polymerase E9, the processivity factor A20, the uracil-DNA glycosylase D4, and the helicase-primase D5. We present the recombinant expression and biochemical and biophysical characterizations of these proteins and the complexes they form. We show that the A20D4 polymerase cofactor binds to E9 with high affinity, leading to the formation of the A20D4E9 holoenzyme. Small-angle X-ray scattering yielded envelopes for E9, A20D4, and A20D4E9. They showed the elongated shape of the A20D4 cofactor, leading to a 150-Å separation between the polymerase active site of E9 and the DNA-binding site of D4. Electron microscopy showed a 6-fold rotational symmetry of the helicase-primase D5, as observed for other SF3 helicases. These results favor a rolling-circle mechanism of vaccinia virus genome replication similar to the one suggested for tailed bacteriophages.

scholarly journals Major Neutralizing Sites on Vaccinia Virus Glycoprotein B5 Are Exposed Differently on Variola Virus Ortholog B6

2007 ◽  
Vol 81 (15) ◽  
pp. 8131-8139 ◽  
Author(s):  
Lydia Aldaz-Carroll ◽  
Yuhong Xiao ◽  
J. Charles Whitbeck ◽  
Manuel Ponce de Leon ◽  
Huan Lou ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Protective Efficacy ◽  
Polyclonal Antibodies ◽  
Passive Immunization ◽  
Variola Virus ◽  
Subunit Vaccines ◽  
Structural And Functional Properties ◽  
Antigenic Properties ◽  
Control And Prevention ◽  
A Subunit

ABSTRACT Immunization against smallpox (variola virus) with Dryvax, a live vaccinia virus (VV), was effective, but now safety is a major concern. To overcome this issue, subunit vaccines composed of VV envelope proteins from both forms of infectious virions, including the extracellular enveloped virion (EV) protein B5, are being developed. However, since B5 has 23 amino acid differences compared with its B6 variola virus homologue, B6 might be a better choice for such a strategy. Therefore, we compared the properties of both proteins using a panel of monoclonal antibodies (MAbs) to B5 that we had previously characterized and grouped according to structural and functional properties. The B6 gene was obtained from the Centers for Disease Control and Prevention, and the ectodomain was cloned and expressed in baculovirus as previously done with B5, allowing us to compare the antigenic properties of the proteins. Polyclonal antibodies to B5 or B6 cross-reacted with the heterologous protein, and 16 of 26 anti-B5 MAbs cross-reacted with B6. Importantly, 10 anti-B5 MAbs did not cross-react with B6. Of these, three have important anti-VV biologic properties, including their ability to neutralize EV infectivity and block comet formation. Here, we found that one of these three MAbs protected mice from a lethal VV challenge by passive immunization. Thus, epitopes that are present on B5 but not on B6 would generate an antibody response that would not recognize B6. Assuming that B6 contains similar variola virus-specific epitopes, our data suggest that a subunit vaccine using the variola virus homologues might exhibit improved protective efficacy against smallpox.

scholarly journals Evasion of the Innate Immune Type I Interferon System by Monkeypox Virus

2015 ◽  
Vol 89 (20) ◽  
pp. 10489-10499 ◽  
Author(s):  
William D. Arndt ◽  
Samantha Cotsmire ◽  
Kelly Trainor ◽  
Heather Harrington ◽  
Kevin Hauns ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Immune Evasion ◽  
Innate Immune ◽  
Type I ◽  
Variola Virus ◽  
Antiviral Protein ◽  
Protein Kinase R ◽  
Monkeypox Virus ◽  
A Genome ◽  
Innate Immune Evasion

ABSTRACTThe vaccinia virus (VACV) E3 protein has been shown to be important for blocking activation of the cellular innate immune system and allowing viral replication to occur unhindered. Mutation or deletion of E3L severely affects viral host range and pathogenesis. While the monkeypox virus (MPXV) genome encodes a homologue of the VACV E3 protein, encoded by the F3L gene, the MPXV gene is predicted to encode a protein with a truncation of 37 N-terminal amino acids. VACV with a genome encoding a similarly truncated E3L protein (VACV-E3LΔ37N) has been shown to be attenuated in mouse models, and infection with VACV-E3LΔ37N has been shown to lead to activation of the host antiviral protein kinase R pathway. In this report, we present data demonstrating that, despite containing a truncated E3 homologue, MPXV phenotypically resembles a wild-type (wt) VACV rather than VACV-E3LΔ37N. Thus, MPXV appears to contain a gene or genes that can suppress the phenotypes associated with an N-terminal truncation in E3. The suppression maps to sequences outside F3L, suggesting that the suppression is extragenic in nature. Thus, MPXV appears to have evolved mechanisms to minimize the effects of partial inactivation of its E3 homologue.IMPORTANCEPoxviruses have evolved to have many mechanisms to evade host antiviral innate immunity; these mechanisms may allow these viruses to cause disease. Within the family of poxviruses, variola virus (which causes smallpox) is the most pathogenic, while monkeypox virus is intermediate in pathogenicity between vaccinia virus and variola virus. Understanding the mechanisms of monkeypox virus innate immune evasion will help us to understand the evolution of poxvirus innate immune evasion capabilities, providing a better understanding of how poxviruses cause disease.

scholarly journals THE STABILITY OF VARIOLA VIRUS PROPAGATED IN EMBRYONATED EGGS

1943 ◽  
Vol 78 (4) ◽  
pp. 231-239 ◽  
Author(s):  
John B. Nelson
Keyword(s):  
Vaccinia Virus ◽  
Significant Alteration ◽  
Variola Virus ◽  
Species Identity ◽  
Apparent Change ◽  
The Stability

After 24 transfers in embryonated eggs a strain of variola virus (Chinese) was established in the testis of the rabbit and maintained for 11 passages at intervals of 7 days. Residence in the rabbit testis was not accompanied by any significant alteration in the species identity of the virus. A second strain of variola virus (Minnesota) was transferred 180 times in embryonated eggs with no apparent change in its behavior. Subsequent attempts, however, to maintain this strain in the rabbit by serial testicular passage were unsuccessful. These observations are discussed in relation to the so called transformation of variola to vaccinia virus by animal passage.

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