title: HIV-1 co-receptor usage based on V3 loop sequence analysis: preferential suppression of CXCR4 virus post HAART?
abstract: Disease progression during human immunodeficiency virus type 1 (HIV-1) infection has been associated with a switch of viral coreceptor usage from CCR5 to CXCR4. The current study investigates the effect of anti retroviral therapy (ART) on the viral tropism in a group of patients based on the V3 loop sequence, in ART naïve patients prior to and 24 weeks after ART. Genomic DNA was extracted from the PBMCs of these patients, and the C2-V5 region of the HIV-1 env genes were cloned and sequenced. The coreceptor usage was predicated based on V3 loop amino acid sequences using Geno2pheno and PSSM programs. Our results indicate that following ART, the plasma viral loads of both CXCR4 and CCR5 viruses were significantly decreased. We observed a relatively higher ratio of R5 than X4 virus after 24 weeks of ART and both the positive charges and the net charges of the V3 regions were decreased significantly (p < 0.05) after ART. We conclude that ART significantly, reduced both X4 and R5 viruses with a preferential suppression of X4 virus. These data will help improve prognostic outcomes and help clinicians determine the course of treatment in patients who exhibit virologic failure while taking a CCR5 antagonist.
authors.affiliation: Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijng 100069, Peoples Republic of China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Jiao
authors.forename: Pengfei
authors.initials: P
authors.lastname: Wang
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Huanzhang
authors.initials: H
authors.lastname: Zhu
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
mesh_terms: D000328:Adult; D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence / Q000235:genetics; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D004279:DNA, Viral / Q000737:chemistry; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics*; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D055672:Static Electricity; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D056189:Viral Tropism / Q000187:drug effects* / Q000235:genetics; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; C527276:CXCR4 protein, human; D004279:DNA, Viral; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019713:Receptors, CCR5; D019718:Receptors, CXCR4