Coreceptor Usage of Human Immunodeficiency Virus Type 1 Strains in Ibadan, Nigeria
E. Donbraye
Department of Medical Microbiology and Parasitology, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria and Department of Virology, College of Medicine, University College Hospital, Ibadan, Oyo State, Nigeria
G. N. Odaibo
Department of Virology, College of Medicine, University College Hospital, Ibadan, Oyo State, Nigeria
D. O. Olaleye *
Department of Virology, College of Medicine, University College Hospital, Ibadan, Oyo State, Nigeria
*Author to whom correspondence should be addressed.
Abstract
Aims: To evaluate HIV-1 Coreceptor usage in Nigeria.
Study Design: Cross-sectional study.
Place and Duration of Study: Department of Virology, College of Medicine, University College Hospital, Ibadan from January 2004 to December 2006.
Methodology: Genomic DNA was extracted from blood samples of 85 (42 males, 43 females; age range 18-58 years) consenting HIV-1 infected antiretroviral therapy-naïve individuals presenting at a voluntary counseling and testing centre. The env C2-V3 region of HIV-1 proviral DNA was amplified by nested PCR, successfully sequenced, manually edited and evolutionary relationships determined by maximum likelihood using MEGA 5.03R from 64 of the blood samples of the HIV-1 infected patients. HIV-1 coreceptor usage was predicted based on genotypic analysis of HIV-1 env V3 loop sequences.
Results: Phylogenetic analysis showed HIV-1 subtypes A, G, CRF02_AG, CRF06_cpx, and CRF35_AD among the study participants The V3 loop region of the viruseshad amino acid sequence conservation in the base positions 1-8 and 26-35 and tip regions and sequence variability, including mutations and deletions at positions 9-25. Most (76.6%) of the sequences had the GPGQ crown motif while the GPGQ/L/R/K substitution was observed in 18.8%. The number of N-linked glycosylation sites ranged from 0 to 4 per env C2-V3 amino acid sequence with only 37.5% of the sequences having all 4 N-linked glycosylation sites. Predicted frequencies for CCR5 and CXCR4 genotypes were 31.2% and 68.8%, respectively, while 10% of the CCR5-tropic viruses showed Maraviroc-associated resistant mutations.
Conclusion: CXCR4-tropic viruses predominate among the studied population irrespective of HIV-1 subtype and and it is associated with multiple amino acid deletions and mutations in V3 and the loss of one or more N-linked glycosylation sites. This data suggest the need for further studies involving a larger sample size prior to introduction of coreceptor inhibitors like Maraviroc for management of HIV infection in Nigeria
Keywords: Coreceptor usage, HIV-1 strains, CCR5, CXCR4, C2-V3 region, V3 loop