tailieunhanh - Báo cáo y học: "Comparative whole genome sequence analysis of wild-type and cidofovir-resistant monkeypoxvirus"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Comparative whole genome sequence analysis of wild-type and cidofovir-resistant monkeypoxvirus | Farlow et al. Virology Journal 2010 7 110 http content 7 1 110 VIROLOGY JOURNAL RESEARCH Open Access Comparative whole genome sequence analysis of wild-type and cidofovir-resistant monkeypoxvirus Jason Farlow Mohamed Ait Ichou John Huggins and Sofi Ibrahim Abstract We performed whole genome sequencing of a cidofovir S -1- 3-hydroxy-2-phosphonylmethoxy-propyl cytosine HPMPC -resistant CDV-R strain of Monkeypoxvirus MPV . Whole-genome comparison with the wild-type WT strain revealed 55 single-nucleotide polymorphisms SNPs and one tandem-repeat contraction. Over one-third of all identified SNPs were located within genes comprising the poxvirus replication complex including the DNA polymerase RNA polymerase mRNA capping methyltransferase DNA processivity factor and poly-A polymerase. Four polymorphic sites were found within the DNA polymerase gene. DNA polymerase mutations observed at positions 314 and 684 in MPV were consistent with CDV-R loci previously identified in Vaccinia virus VACV . These data suggest the mechanism of CDV resistance may be highly conserved across Orthopoxvirus OPV species. SNPs were also identified within virulence genes such as the A-type inclusion protein serine protease inhibitor-like protein SPI-3 Schlafen ATPase and thymidylate kinase among others. Aberrant chain extension induced by CDV may lead to diverse alterations in gene expression and viral replication that may result in both adaptive and attenuating mutations. Defining the potential contribution of substitutions in the replication complex and RNA processing machinery reported here may yield further insight into CDV resistance and may augment current therapeutic development strategies. Background Poxviruses are large enveloped pleomorphic dsDNA viruses that infect a diverse array of mammals reptiles and insects 1 . The causative agent of Smallpox Variola virus VARV is a member of the OPV genus. Smallpox was declared eradicated in 1980 however natural or illicit .