The Orthopoxviruses (OPVs) comprise a group of viruses that possess very similar genomes; they vary considerably, however, in virulence. Among them, rabbitpox virus (RPXV) and monkeypox virus (MPXV) are the focus of this thesis. RPXV is closely related to vaccinia virus (VACV) but is significantly more virulent in rabbits. The West African isolates of MPXV, which also caused the human monkeypox 2003 outbreak in the USA. have different disease profiles from the Central African MPXV. To determine the basis for these differences, the complete genomes of RPXV-UTR and three West African isolates of MPXV were sequenced and analyzed.
The result of the RPXV study indicates that 3 RPXV genes. alone or in combination. likely play a key role in the enhanced RPXV-UTR virulence over VACV isolates. These genes encode: the RING finger protein (RPXV-UTR 008), an ankyrin repeat family protein (RPXV-UTR 180) and the chemokine binding protein (RPXV-UTR 001/184) in the inverted terminal repeats (ITR) of RPXV.
Examination of the evolutionary relationship between RPXV-UTR and other OPVs was carried out using the central DNA sequence of the genome that is conserved among all completely sequenced OPVs and also the protein sequences derived from the 49 genes present in all completely sequenced Chordopoxviruses (ChPV). The results of these analyses both confirm the hypothesis that RPXV-UTR is most similar to VACV.
An animal study found that the Central African MPXV isolate is more virulent than the West African MPXV isolate. The comparison of the three West African isolates MPXV-COP-58. MPXV-SL-V70. and MPXV-WRAIR, and the Congo basin (Central Africa) isolate MPXV-ZAI-96-I-16 shows that the MPXV-ZAI-96-I-16 ORF D14L, which encodes an inhibitor of human complement, is most likely the virulence gene responsible for the pathogenesis differences between the West and Central African isolates. These results explain the lack of fatalities in the 2003 MPXV outbreak in the USA, which was caused by importation of a West African MPXV isolate.
| Identifer | oai:union.ndltd.org:uvic.ca/oai:dspace.library.uvic.ca:1828/1977 |
| Date | 15 December 2009 |
| Creators | Li, Guiyun |
| Contributors | Upton, Christopher |
| Source Sets | University of Victoria |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Rights | Available to the World Wide Web |
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