DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Comprehensive Genetic Characterization of Four Novel HIV-1 Circulating Recombinant Forms (CRF129_56G, CRF130_A1B, CRF131_A1B, and CRF138_cpx): Insights from Molecular Epidemiology in Cyprus

Journal Article · · Viruses
DOI: https://doi.org/10.3390/v16010019 · OSTI ID:2470549

Molecular investigations of the HIV-1 pol region (2253–5250 in the HXB2 genome) were conducted on sequences obtained from 331 individuals infected with HIV-1 in Cyprus between 2017 and 2021. This study unveiled four distinct HIV-1 putative transmission clusters, encompassing 19 previously unidentified HIV-1 recombinants. These recombinants, each comprising eight, three, four, and four sequences, respectively, did not align with previously established Circulating Recombinant Forms (CRFs). To characterize these novel HIV-1 recombinants, near-full-length genome sequences were successfully obtained for 16 of the 19 recombinants (790–8795 in the HXB2 genome) using an in-house-developed RT-PCR assay. Phylogenetic analyses, employing MEGAX and Cluster-Picker, along with confirmatory neighbor-joining tree analyses of subregions, were conducted to identify distinct clusters and determine subtypes. The uniqueness of the HIV-1 recombinants was evident in their exclusive clustering within generated maximum likelihood trees. Recombination analyses highlighted the distinct chimeric nature of these recombinants, with consistent mosaic patterns observed across all sequences within each of the four putative transmission clusters. Conclusive genetic characterization identified four novel HIV-1 CRFs: CRF129_56G, CRF130_A1B, CRF131_A1B, and CRF138_cpx. CRF129_56G exhibited two recombination breakpoints and three fragments of subtypes CRF56_cpx and G. Both CRF130_A1B and CRF131_A1B featured seven recombination breakpoints and eight fragments of subtypes A1 and B. CRF138_cpx displayed five recombination breakpoints and six fragments of subtypes CRF22_01A1 and F2, along with an unclassified fragment. Additional BLAST analyses identified a Unique Recombinant Form (URF) of CRF138_cpx with three additional recombination sites, involving subtype F2, a fragment of unknown subtype origin, and CRF138_cpx. Post-identification, all putative transmission clusters remained active, with CRF130_A1B, CRF131_A1B, and CRF138_cpx clusters exhibiting further growth. Furthermore, international connections were identified through BLAST analyses, linking one sequence from the USA to the CRF130_A1B strain, and three sequences from Belgium and Cameroon to the CRF138_cpx strain. This study contributes valuable insights into the dynamic landscape of HIV-1 diversity and transmission patterns, emphasizing the need for ongoing molecular surveillance and global collaboration in tracking emerging viral variants.

Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
89233218CNA000001
OSTI ID:
2470549
Journal Information:
Viruses, Journal Name: Viruses Journal Issue: 1 Vol. 16; ISSN 1999-4915
Publisher:
MDPICopyright Statement
Country of Publication:
United States
Language:
English

References (31)

Recombination in AIDS viruses journal March 1995
A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences journal June 1980
Global and regional epidemiology of HIV-1 recombinants in 1990–2015: a systematic review and global survey journal November 2020
Automated subtyping of HIV-1 genetic sequences for clinical and surveillance purposes: Performance evaluation of the new REGA version 3 and seven other tools journal October 2013
Development of a new comprehensive HIV-1 genotypic drug resistance assay for all commercially available reverse transcriptase, protease and integrase inhibitors in patients infected with group M HIV-1 strains journal July 2020
High frequency of new recombinant forms in HIV-1 transmission networks demonstrated by full genome sequencing journal October 2020
HIV-1 Infection in Cyprus, the Eastern Mediterranean European Frontier: A Densely Sampled Transmission Dynamics Analysis from 1986 to 2012 journal January 2018
Characterization of a novel HIV-1 circulating recombinant form, CRF91_cpx, comprising CRF02_AG, G, J, and U, mostly among men who have sex with men journal August 2022
Web Resources for HIV Type 1 Genotypic-Resistance Test Interpretation journal June 2006
A Computer Program Designed to Screen Rapidly for HIV Type 1 Intersubtype Recombinant Sequences journal November 1995
Genetic Analysis of HIV Type 1 Strains from Newly Infected Untreated Patients in Cyprus: High Genetic Diversity and Low Prevalence of Drug Resistance journal January 2009
Near Full-Length Genetic Analysis of HIV Sequences Derived from Cyprus: Evidence of a Highly Polyphyletic and Evolving Infection journal August 2009
Molecular Characterization of HIV Type 1 Strains from Newly Diagnosed Patients in Cyprus (2007–2009) Recovers Multiple Clades Including Unique Recombinant Strains and Lack of Transmitted Drug Resistance journal November 2011
AliView: a fast and lightweight alignment viewer and editor for large datasets journal August 2014
Near full-length HIV type 1M genomic sequences from Cameroon: Evidence of early diverging under-sampled lineages in the country journal January 2015
MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms journal May 2018
CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice journal January 1994
jpHMM: Improving the reliability of recombination prediction in HIV-1 journal May 2009
HIV subtype diversity worldwide journal January 2019
Brief Report: Complete Genome Sequence of CG-0018a-01 Establishes HIV-1 Subtype L journal March 2020
Re-analysis of human immunodeficiency virus type 1 isolates from Cyprus and Greece, initially designated ‘subtype I’, reveals a unique complex A/G/H/K/? mosaic pattern journal March 2001
HIV-1 Nomenclature Proposal journal April 2000
Sequence Evaluation and Comparative Analysis of Novel Assays for Intact Proviral HIV-1 DNA journal February 2021
An Isolate of Human Immunodeficiency Virus Type 1 Originally Classified as Subtype I Represents a Complex Mosaic Comprising Three Different Group M Subtypes (A, G, and I) journal December 1998
Full-Length Human Immunodeficiency Virus Type 1 Genomes from Subtype C-Infected Seroconverters in India, with Evidence of Intersubtype Recombination journal January 1999
HIV-1 Genetic Variability and Clinical Implications journal June 2013
The HIVdb System for HIV-1 Genotypic Resistance Interpretation journal January 2012
Automated analysis of phylogenetic clusters journal November 2013
Utility of Metagenomic Next-Generation Sequencing for Characterization of HIV and Human Pegivirus Diversity journal November 2015
HIV-1 transmission networks across Cyprus (2010-2012) journal April 2018
Comparative HIV-1 Phylogenies Characterized by PR/RT, Pol and Near-Full-Length Genome Sequences journal October 2022