Human monkeypox and smallpox viruses: genomic comparison

Abstract

Monkeypox virus (MPV) causes a human disease which resembles smallpox but with a lower person-to-person transmission rate. To determine the genetic relationship between the orthopoxviruses causing these two diseases, we sequenced the 197-kb genome of MPV isolated from a patient during a large human monkeypox outbreak in Zaire in 1996. The nucleotide sequence within the central region of the MPV genome, which encodes essential enzymes and structural proteins, was 96.3% identical with that of variola (smallpox) virus (VAR). In contrast, there were considerable differences between MPV and VAR in the regions encoding virulence and host-range factors near the ends of the genome. Our data indicate that MPV is not the direct ancestor of VAR and is unlikely to naturally acquire all properties of VAR. ß 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

Identification of the Orthopoxvirus p4c Gene, Which Encodes a Structural Protein That Directs Intracellular Mature Virus Particles into A-Type Inclusions

“…First, this portion of the cowpox virus P4c protein contains the region predicted to contain 28 consecutive aspartic acid residues. A similarly positioned tract of 23 aspartic acids is present in the predicted sequence of the monkeypox virus P4c protein (65). However, this region is absent from the P4c proteins of variola virus and vaccinia virus, showing that this polyaspartate tract is not required for the V ϩ phenotype.…”

“…The p4c gene is present as open reading frame A28L in monkeypox virus strain Zaire-96-I-16, where it is predicted to encode a protein with ϳ91% (476 of 520 amino acids) identity to the vaccinia virus P4c protein (65). It is present in camelpox virus M-96 (19), where it is predicted to show 95% identity (476 of 500 amino acids) to the vaccinia virus P4c protein.…”

Inhibition of CD1d1‐mediated antigen presentation by the vaccinia virus B1R and H5R molecules

“…The ability of B1R and H5R to reduce the innate immune response in relation to CD1d1-mediated antigen presentation to NKT cells has applications concerning the development of more effective vaccines against variola virus, the causative agent of smallpox, and for which VV has been the poxvirus of choice for a vaccine backbone. Both B1R and H5R genes are present in variola virus [26], and are also found in other orthopoxviruses such as monkeypox [27]. It has been shown in a number of systems that NKT cells bridge the .…”

Real-Time PCR System for Detection of Orthopoxviruses and Simultaneous Identification of Smallpox Virus

“…Historically, differentiation of OPVs into single species has been achieved by biological means, such as pock morphology on the chorioallantoic membrane or ceiling growth temperature, because serological tests proved to be of limited value (3). DNA maps and several other molecular biologic features, including full genome sequencing, have been applied and have provided definitive information for virus classification (4,24,25,26). Various PCR methods have been used to identify and subtype the available OPVs by using consensus primers combined with restriction cleavage and/or sequencing of amplicons (6,10,13,18,23) or oligonucleotidebased microchip technology (11,12,20).…”