Virological characterization of HIV-1 CA-NTD mutants constructed in a virus-lineage reflected manner

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  • Nakanishi Shoko
    Department of Microbiology, Tokushima University Graduate School of Medical Science
  • Watanabe Sakimi
    Department of Microbiology, Tokushima University Graduate School of Medical Science
  • Doi Naoya
    Department of Microbiology, Tokushima University Graduate School of Medical Science
  • Koma Takaaki
    Department of Microbiology, Tokushima University Graduate School of Medical Science
  • Adachi Akio
    Department of Microbiology, Kansai Medical University
  • Nomaguchi Masako
    Department of Microbiology, Tokushima University Graduate School of Medical Science

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  • Virological characterization of HIV‐1 CA‐NTD mutants constructed in a virus‐lineage reflected manner

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<p>Capsid (CA) protein is a major virion‐constituent of all retroviruses including human immunodeficiency virus type 1 (HIV‐1), and is essential for early and late phases in viral replication cycle through interaction with numerous cellular factors. In particular, N‐terminal domain (NTD) of HIV‐1 CA has been frequently and well reported to bind to various host cell proteins that considerably affect viral replication potential. In this study, in order to better define biological bases of the CA‐NTD for HIV‐1 replication, we performed an extensive mutational analysis in an unprecedented manner. By aligning CA‐NTD sequences derived from representative infectious molecular clones of HIV‐1, HIV‐2, and simian immunodeficiency virus isolated from the rhesus macaque (SIVmac), a number of amino acids specific to HIV‐1 were selected, and were replaced with those from SIVmac at the corresponding sites. Mutant viruses thus generated were then examined for multi‐cycle infectivity, single‐cycle infectivity, and ability to produce progeny virions. While some CA‐NTD mutations affected viral replication ability to varying degrees, those in helix 7 abolished viral growth potential without exception. These results highlight functional importance of non‐conserved amino acids in helix 7, and give new insights into functionality of HIV‐1 CA‐NTD. J. Med. Invest. 65:110‐115, February, 2018</p>

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