HIV-1 B-subtype capsid protein: a characterization of amino acid's conservation and its significant association with integrase signatures.
The HIV-1 pre-integration phase and the subsequent integration of viral genome to the host of nuclear chromosomes are not well analyzed so far. Many studies are discussing the question of pre- and post-nuclear viral entry which is to support the assumption that HIV-1 integrase (IN) is maintained in the volume of intact conical structure's capsids through HIV entry. The aim of the current study is to identify the prevalence of capsid's (CA) signatures among drug-naïve and antiretroviral (ARV)-treated patients in a cohort of 827 HIV-1 B-subtype-infected individuals, and subsequently the relationship between IN and CA amino acid's changes was evaluated. These analyses suggest a conceivable co-evolution of IN-CA sequences, especially in relation to steps of nuclear viral entry. The frequency of mutations was calculated, and statistically has been compared between treatment-naïve and ARV-treated patients. The binomial correlation coefficient was used to assess covariation among CA and IN mutations; then, the average linkage hierarchical agglomerative clustering was performed. The results show a detailed conservation of HIV-1 CA protein both in drug-naïve and in ARV-treated patients. Moreover, the specific CA substitutions are significantly associated with different IN signatures at the amino acid level and the topology of the dendrogram has revealed the existence of two strong sub-clusters associated with hypothetical different mutational pathways. The in vitro and in vivo studies are necessary to exclude the hypothetical statistical false positive results and in order to confirm that some CA amino acid signatures are going to establish specific and precise implication in the HIV life cycle.
BioMolecular Lab, Barletta, BT, Italy, salvatore.dimonte@gmail.com.
Salvatore
S
Dimonte
Muhammed
M
Babakir-Mina
Stefano
S
Aquaro
D000328:Adult; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000627:therapeutic use; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D019427:HIV Integrase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000145:classification / Q000201:enzymology / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D053586:Virus Internalization
D019380:Anti-HIV Agents; D036022:Capsid Proteins; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1