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HIV-1 B-subtype capsid protein: a characterization of amino acid’s conservation and its significant association with integrase signatures

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Abstract

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.

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Acknowledgments

Many thanks to Stefania Carmen Spinazzola and Bahra Rzgar Abdullah for their excellent technical assistance and Dana Hameed Mahmood and Prof. Domenico Sturino for punctuation and grammatical revision.

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Authors and Affiliations

  1. BioMolecular Lab, Barletta, BT, Italy

    Salvatore Dimonte

  2. Biomedical Research Center, Sulaimani Polytechnic University, Iraqi Kurdistan Region, Sulaymaniyah, Iraq

    Muhammed Babakir-Mina

  3. Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende, CS, Italy

    Stefano Aquaro

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  1. Salvatore Dimonte
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  2. Muhammed Babakir-Mina
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Correspondence to Salvatore Dimonte.

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Dimonte, S., Babakir-Mina, M. & Aquaro, S. HIV-1 B-subtype capsid protein: a characterization of amino acid’s conservation and its significant association with integrase signatures. Virus Genes 48, 429–437 (2014). https://doi.org/10.1007/s11262-014-1039-y

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