Changes in dynamic and static structures of the HIV ‐1 p24 capsid protein N‐domain caused by amino‐acid substitution are associated with its viral viability

2021 ◽  
Author(s):  
Yusuke Sato ◽  
Akimasa Matsugami ◽  
Satoru Watanabe ◽  
Fumiaki Hayashi ◽  
Munehito Arai ◽  
...  
Author(s):  
Ameeruddin Nusrath Unissa ◽  
Luke Elizabeth Hanna

Reverse transcriptase (RT) is a vital enzyme in the process of transcription of HIV-1. The nucleoside analogues of RT inhibitors (NRTIs) act by substrate competition and chain termination as they resemble a nucleotide. To understand the basis of RT resistance in HIV-1, in this chapter, one of the clinically essential mutants Q151M of RT which exhibits multi-resistance to many NRTIs was modeled and docked with NRTIs in comparison to wild type (WT). The results of docking indicate that the WT showed high affinity with all inhibitors compared to the mutant (MT). It can be suggested that the high affinity in WT could be attributed to the favorable interactions with all inhibitors that lacks in MT due to amino acid substitution that leads to structural changes in MT protein, which alters the favorable network of interaction and eventually imparts resistance to all inhibitors.


2009 ◽  
Vol 84 (2) ◽  
pp. 976-982 ◽  
Author(s):  
Chien-Cheng Chiang ◽  
Shiu-Mei Wang ◽  
Yen-Yu Pan ◽  
Kuo-Jung Huang ◽  
Chin-Tien Wang

ABSTRACT HIV-1 protease (PR) mediates the proteolytic processing of virus particles during or after virus budding. PR activation is thought to be triggered by appropriate Gag-Pol/Gag-Pol interaction; factors affecting this interaction either enhance or reduce PR-mediated cleavage efficiency, resulting in markedly reduced virion production or the release of inadequately processed virions. We previously showed that a Gag-Pol deletion mutation involving the reverse transcriptase tryptophan (Trp) repeat motif markedly impairs PR-mediated virus maturation and that an alanine substitution at W401 (W401A) or at both W401 and W402 (W401A/W402A) partially or almost completely negates the enhancement effect of efavirenz (a nonnucleoside reverse transcriptase inhibitor) on PR-mediated virus processing efficiency. These data suggest that the Trp repeat motif may contribute to the PR activation process. Here we demonstrate that due to enhanced Gag cleavage efficiency, W402 alanine or leucine substitution significantly reduces virus production. However, W402 replacement with phenylalanine does not significantly affect virus particle assembly or processing, but it does markedly impair viral infectivity in a single-cycle infection assay. Our results demonstrate that a single amino acid substitution at HIV-1 RT can radically affect virus assembly by enhancing Gag cleavage efficiency, suggesting that in addition to contributing to RT biological function during the early stages of virus replication, the HIV-1 RT tryptophan repeat motif in a Gag-Pol context may play an important role in suppressing the premature activation of PR during late-stage virus replication.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Cinzia Giagulli ◽  
Pasqualina D’Ursi ◽  
Wangxiao He ◽  
Simone Zorzan ◽  
Francesca Caccuri ◽  
...  

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