The RNA binding G-patch domain in retroviral protease is important for infectivity and D-type morphogenesis of Mason-Pfizer monkey virus.
Retroviral proteases (PRs) cleave the viral polyprotein precursors into functional mature proteins late during particle release and are essential for viral replication. Unlike most retroviruses, beta-retroviruses, including Mason-Pfizer monkey virus (M-PMV), assemble immature capsids within the cytoplasm of the cell. The activation of beta-retroviral proteases must be highly regulated, because processing of the Gag-related polyprotein precursors occurs only after transport of immature capsids to the plasma membrane and budding. Several beta-retroviral proteases have unique C-terminal extension sequences, containing a glycine-rich motif (G-patch), which specifically binds in vitro to single-stranded nucleic acids. In M-PMV PR the G-patch is removed in vitro as well as in vivo by autoproteolytic processing to yield truncated active forms of PR. To investigate the role of the G-patch domain on the virus life cycle, we introduced mutations within the C-terminal domain of protease. We found that the G-patch domain of M-PMV PR is not required for the processing of viral polyproteins, but it significantly influences the infectivity of M-PMV, the activity of reverse transcriptase, and assembly of immature capsid within the cells. These results demonstrate for the first time that the G-patch domain of M-PMV PR is critical for the life cycle of beta-retroviruses, and its evolutionary conservation within members of this genus suggests its importance for retroviruses that display D-type morphology.
Bauerová-Zábranská
Helena
H
Centre for New Antivirals and Antineoplastics, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague.
Stokrová
Jitka
J
Strísovsky
Kvido
K
Hunter
Eric
E
Ruml
Tomás
T
Pichová
Iva
I
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D016093:Mason-Pfizer monkey virus / Q000201:enzymology / Q000472:pathogenicity*; D008969:Molecular Sequence Data; D009024:Morphogenesis; D016296:Mutagenesis; D010447:Peptide Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014774:Virulence
D012367:RNA, Viral; D012194:RNA-Directed DNA Polymerase; D010447:Peptide Hydrolases