Journal
VIRUSES-BASEL
Volume 14, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/v14122687
Keywords
HIV-1; integrase; RNase H; virus release; autoprocessing; maturation
Categories
Funding
- National Cancer Institute, National Institutes of Health
- National Institute of Allergy and Infectious Disease [HHSN261200800001E]
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The defect in HIV(IN:M50I/V151I) virus release and autoprocessing initiation is regulated by the C-terminal domains of RNase H and integrase. Specifically, aspartic acid at codon 109 of RNase H C-terminal domain and aspartic acid at the C terminus of integrase induce the defect.
Previously, we reported that an HIV-1 variant containing Met-to-Ile change at codon 50 and Val-to-Ile mutation at codon 151 of integrase (IN), HIV(IN:M50I/V151I), was an impaired virus. Despite the mutations being in IN, the virus release was significantly suppressed (p < 0.0001) and the initiation of autoprocessing was inhibited; the mechanism of the defect remains unknown. In the current study, we attempted to identify the critical domains or amino acid (aa) residue(s) that promote defects in HIV(IN:M50I/V151I), using a series of variants, including truncated or aa-substituted RNase H (RH) or IN. The results demonstrated that virus release and the initiation of autoprocessing were regulated by the C-terminal domains (CTDs) of RH and IN. Further studies illustrated that Asp at codon 109 of RH CTD and Asp at the C terminus of IN induces the defect. This result indicated that the CTDs of RH and IN in GagPol and particular aa positions in RH and IN regulated the virus release and the initiation of autoprocessing, and these sites could be potential targets for the development of new therapies.
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