The C-terminal domain of RNase H and the C-terminus amino acid residue regulate virus release and autoprocessing of a defective HIV-1 possessing M50I and V151I changes in integrase

Imamichi, T.; Chen, C.; Hao, M.; Chang, W.; Yang, Y.

doi:10.1101/2022.10.23.513430

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bioRxiv · 10.1101/2022.10.23.513430

The C-terminal domain of RNase H and the C-terminus amino acid residue regulate virus release and autoprocessing of a defective HIV-1 possessing M50I and V151I changes in integrase

Imamichi, T.·Chen, C.·Hao, M.·Chang, W.·Yang, Y.

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Abstract

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 CTD 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 developing new therapies.

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Imamichi, T., Chen, C., Hao, M., Chang, W., Yang, Y.. 2022-10-24. The C-terminal domain of RNase H and the C-terminus amino acid residue regulate virus release and autoprocessing of a defective HIV-1 possessing M50I and V151I changes in integrase. https://doi.org/10.1101/2022.10.23.513430

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