Variability and Signatures of Capsid Amino Acid of HIV-1D Subtype from Drug-Naive and ARV-treated Individuals

Objective

The infection by the human immunodeficiency virus (HIV) has changed dramatically in recent years from invariably fatal disease to chronic disease. HIV-1 subtype D viruses were first isolated from the peripheral blood lymphocytes in 1983 in patients from the Democratic Republic of the Congo and today this subtype is present mainly in eastern, central and west Africa. There are fewer studies that expansively investigate the HIV-1 subtype D diversity for capsid variability to date thus in this study wanted to analyse and examine the distribution of naturally occurring sequence variability in full-length capsid sequences of HIV-1 subtype D.

Methods

The 279 HIV-1 D-subtype capsid sequences from the Los Alamos database were retrieved. From this conspicuous dataset of patients at all stages of infection (one isolate per single patient), 153 were drug-naïve and 126 were drug-treated. Then, the amino acidic variability of capsid sequences was analysed.

Results 

In drug-naïve patients, among the 80 capsid variable residues, 27 were mutated in >5 % of patients and 9 of them were highly variable. Consequently, 151 out of 231 capsid amino acid residues were highly conserved (≤1 % variability). While in ARV-treated patients, among the 83 variable residues, 29 were mutated in >5 % of patients, and 11 of them were highly variable. Consequently, 148 out of 231 capsid amino acid residues were highly conserved (≤1 % variability).

Conclusion

Genetic fragility of the HIV-1 capsid may explain why cell-mediated immune responses to Gag link with better prognosis in viral infection, and suggests that viral capsids are the good targets for therapy as well as vaccination strategies. Hence, the variability of the capsid protein of the D-subtype HIV-1 is not widespread, but it is absolutely mandatory to prevent minority species resistant to any new treatment approaches. Also the specific in vitro and/or in vivo studies are needed to establish the role of some signatures here noted. Exploring further the implications such changes may have on drug-resistance may be relevant