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Updated: Oct 25, 2025
A Restriction Enzyme Based Cloning Method to Assess the In vitro Replication Capacity of HIV-1 Subtype C Gag-MJ4 Chimeric Viruses
Published on: August 31, 2014
Cuban history of CRF19 recombinant subtype of HIV-1
Anna Zhukova1,2, Jakub Voznica1,3, Miraine Dávila Felipe1,4
1Unité Bioinformatique Evolutive, Département de Biologie Computationelle, Institut Pasteur, Paris, France.
Insights
CRF19, a unique HIV-1 recombinant strain, was introduced to Cuba in the 1970s and spread rapidly, particularly among men who have sex with men. Further research is needed to understand its rapid progression to AIDS.
Area of Science:
- * Virology and Epidemiology
- * Molecular Evolution
- * Public Health
Background:
- * CRF19 is a recombinant form of HIV-1 subtypes D, A1, and G, primarily found in Cuba.
- * It accounts for approximately 25% of new HIV cases in Cuba and is associated with rapid progression to AIDS.
- * The origin and early transmission dynamics of CRF19 in Cuba remain incompletely understood.
Purpose of the Study:
- * To investigate the origin and evolutionary history of the CRF19 HIV-1 subtype.
- * To analyze the spatio-temporal spread and transmission patterns of CRF19 within Cuba.
- * To identify drug resistance mutations and transmission clusters associated with CRF19.
Main Methods:
- * Analysis of approximately 700 pol and env sequences from Cuba and the Los Alamos database.
- * Phylogeny reconstruction and spatio-temporal analysis using fast maximum likelihood approaches.
- * Ancestral character reconstruction for transmission mode and drug resistance mutations, verified with Bayesian methods.
Main Results:
- * CRF19 recombined between 1966 and 1977, likely originating from a Cuban community in the Congo region.
- * The epidemic began in the 1970s in Villa Clara, Cuba, initially spreading through heterosexual contact.
- * Rapid spread occurred in the 1980s within the men who have sex with men (MSM) community, with subsequent transmissions back to heterosexual populations.
Conclusions:
- * CRF19 was introduced to Cuba much earlier than previously thought, contributing to its local epidemiological success.
- * The epidemic's early introduction and founder effect likely influenced its spread patterns.
- * The rapid progression to AIDS associated with CRF19 requires targeted surveillance and further investigation.
Abstract:
CRF19 is a recombinant form of HIV-1 subtypes D, A1 and G, which was first sampled in Cuba in 1999, but was already present there in 1980s. CRF19 was reported almost uniquely in Cuba, where it accounts for ∼25% of new HIV-positive patients and causes rapid progression to AIDS (∼3 years). We analyzed a large data set comprising ∼350 pol and env sequences sampled in Cuba over the last 15 years and ∼350 from Los Alamos database. This data set contained both CRF19 (∼315), and A1, D and G sequences. We performed and combined analyses for the three A1, G and D regions, using fast maximum likelihood approaches, including: (1) phylogeny reconstruction, (2) spatio-temporal analysis of the virus spread, and ancestral character reconstruction for (3) transmission mode and (4) drug resistance mutations (DRMs). We verified these results with a Bayesian approach. This allowed us to acquire new insights on the CRF19 origin and transmission patterns. We showed that CRF19 recombined between 1966 and 1977, most likely in Cuban community stationed in Congo region. We further investigated CRF19 spread on the Cuban province level, and discovered that the epidemic started in 1970s, most probably in Villa Clara, that it was at first carried by heterosexual transmissions, and then quickly spread in the 1980s within the "men having sex with men" (MSM) community, with multiple transmissions back to heterosexuals. The analysis of the transmission patterns of common DRMs found very few resistance transmission clusters. Our results show a very early introduction of CRF19 in Cuba, which could explain its local epidemiological success. Ignited by a major founder event, the epidemic then followed a similar pattern as other subtypes and CRFs in Cuba. The reason for the short time to AIDS remains to be understood and requires specific surveillance, in Cuba and elsewhere.
