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

Cicek Topcu; Vasilis Georgiou; Johana Hezka Rodosthenous; Ioannis Demetriades; Brian Thomas Foley; Leondios G Kostrikis

doi:10.1080/21505594.2022.2106021

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

Virulence. 2022 Dec;13(1):1331-1348. doi: 10.1080/21505594.2022.2106021.

Authors

Cicek Topcu¹, Vasilis Georgiou¹, Johana Hezka Rodosthenous¹, Ioannis Demetriades², Brian Thomas Foley³, Leondios G Kostrikis^{1

4}

Affiliations

¹ Department of Biological Sciences, University of Cyprus, 1 University Avenue, Aglantzia, Nicosia, Cyprus.
² AIDS Clinic, Larnaca General Hospital, Larnaca, Cyprus.
³ Los Alamos National Laboratory, T-6 Theoretical Biology and Biophysics, Los Alamos, NM, USA.
⁴ Cyprus Academy of Sciences, Letters, and Arts, Nicosia, Cyprus.

Abstract

Prospective molecular studies of HIV-1 pol region (2253-5250 in HXB2 genome) sequences from sequenced samples of 269 HIV-1-infected patients in Cyprus (2017-2021) revealed a transmission cluster of 14 unknown HIV-1 recombinants that were not classified as previously established CRFs. The earliest recombinant was collected in September 2017, and the transmission cluster continued to grow until November 2020. Near full-length HIV-1 genome sequences of the 11 of the 14 recombinants were successfully obtained (790-8795 in HXB2 genome) and aligned against a reference dataset of HIV-1 subtypes and CRFs. We employed MEGAX for maximum-likelihood tree construction (GTR model, 1000 bootstrap replicates), Cluster-Picker for phylogenetic clustering analysis (genetic distance ≤0.045, bootstrap support value ≥70%), and REGA-3.0 for subtype determination. Bootscan and similarity plot analyses (sliding window of 400 nucleotides overlapped by 40 nucleotides) were conducted using SimPlot-v3.5.1, and subregion confirmatory neighbour-joining tree analyses were conducted using MEGAX (Kimura two-parameter model, 1000 bootstrap replicates, ≥70% bootstrap-support value). Exclusive clustering of the HIV-1 recombinants revealed their uniqueness. The recombination analyses illustrated the same unique mosaic pattern with six putative intersubtype recombination breakpoints, seven fragments of subtypes CRF02_AG, G, J and an unclassified fragment. We conclusively characterized the mosaic structure of the novel HIV-1 CRF, named CRF91_cpx, by the Los Alamos HIV Sequence Database. Additionally, we identified a URF of CRF91_cpx with two additional recombination sites, generated by a recombination event between subtype B and CRF91_cpx. Since the identification of CRF91_cpx, two additional patient samples have been entered into the CRF91_cpx transmission cluster, demonstrating active growth.

Keywords: Cyprus; HIV-1 genetic diversity; HIV-1 molecular epidemiology; HIV-1 phylogeny; Human immunodeficiency virus type 1; circulating recombinant forms; unique recombinant forms.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Genome, Viral
Genotype
HIV Infections*
HIV-1* / genetics
Homosexuality, Male
Humans
Male
Nucleotides
Phylogeny
Recombination, Genetic
Sequence Analysis, DNA
Sexual and Gender Minorities*

Substances

Nucleotides

Grants and funding

This work was co-funded by the European Regional Development Fund and the Republic of Cyprus through the Research and Innovation Foundation (Project: EXCELLENCE/0918/0093), the Ministry of Health of the Republic of Cyprus (Contract No 240/2019), the University of Cyprus and the Cyprus Academy of Sciences, Letters, and Arts through internal funds awarded to Professor Leondios G. Kostrikis.