Origin, evolution and pathogenesis of CRF19_cpx. A recombinant form of HIV-1 with high prevalence in Cuba
Keywords:
CRF19_cpx, tropismo, patogenia, origen, evoluciónAbstract
Introduction: CRF19_cpx is a recombinant form of HIV-1 subtypes D, A1 and G, which was first reported in Cuban patients. This variant has spread in Cuba and has been associated with rapid progression to AIDS. The objective of this research has been to go deeper into the origin, evolution and pathogenesis of CRF19_cpx. Methods: HIV-1 subtype was determined in 701 samples from the 2014-2019 periods by pol gene sequencing. The relationship between the subtypes and the use of the co-receptor was carried out with 176 plasmas: 107 from the years 2014-2016 and 69 from 2017-2019. The prediction of the viral phenotype (R5, R5X4 or X4) was generated with Geno2pheno, from partial sequences of the envgene. To determine the origin and evolution of CRF19_cpx, 350 partial sequences (pol and env) from Cuban patients and 350 from Los Alamos were used. Analyses were performed using maximum likelihood approaches including: reconstruction of phylogeny, spatio-temporal analysis of virus spread, reconstruction of ancestral character and mode of transmission. Results and discussion: The most frequent HIV-1 subtypes were B, CRF19_cpx and CRF_BG. CRF19_cpx was associated with the use of the CXCR4 co-receptor (p <0.05), being frequent among individuals with a recent diagnosis (36.4%, p = 0.0081). CRF19_cpx was recombined between 1966 and 1977, possibly among the Cuban community stationed in Congo, and was introduced in Cuba in the late 1970s, probably through the province of Villa Clara and then to Havana. It is concluded that the preferential tropism for the CXCR4 co-receptor, detected in CRF19_cpx, accompanied by greater viral replication and unrelated to the time of diagnosis of the patients, reinforces the hypothesis that this viral variant could have greater pathogenicity. Phylogenetic analysis showed a very early introduction of CRF19_cpx in Cuba, which could explain its epidemiological success.
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