title: Patients infected with CRF07_BC have significantly lower viral loads than patients with HIV-1 subtype B: mechanism and impact on disease progression.
abstract: The circulating recombinant form (CRF) 07_BC is the most prevalent HIV-1 strain among injection drug users (IDUs) in Taiwan. It contains a 7 amino-acid deletion in its p6gag. We conducted a cohort study to compare viral loads and CD4 cell count changes between patients infected with subtype B and CRF07_BC and to elucidate its mechanism. Twenty-one patients infected with CRF07_BC and 59 patients with subtype B were selected from a cohort of 667 HIV-1/AIDS patients whom have been followed up for 3 years. Generalized estimated equation was used to analyze their clinical data and the results showed that patients infected with CRF07_BC had significantly lower viral loads (about 58,000 copies per ml less) than patients with subtype B infection (p = 0.002). The replicative capacity of nine CRF07_BC and four subtype B isolates were compared and the results showed that the former had significantly lower replicative capacity than the latter although all of them were CCR5- tropic and non-syncytium inducing viruses. An HIV-1-NL4-3 mutant virus which contains a 7 amino-acid deletion in p6gag (designated as 7d virus) was generated and its live cycle was investigated. The results showed that 7d virus had significantly lower replication capacity, poorer protease-mediated processing and viral proteins production. Electron microscopic examination of cells infected with wild-type or 7d virus demonstrated that the 7d virus had poorer and slower viral maturation processes: more viruses attached to the cell membrane and higher proportion of immature virions outside the cells. The interaction between p6gag and Alix protein was less efficient in cells infected with 7d virus. In conclusion, patients infected with CRF07_BC had significantly lower viral loads than patients infected with subtype B and it may due to the deletion of 7 amino acids which overlaps with Alix protein-binding domain of the p6gag.
authors.affiliation: Center for Infectious Disease and Cancer Research (CICAR), Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Szu-Wei
authors.initials: SW
authors.lastname: Huang
authors.affiliation: Center for Infectious Disease and Cancer Research (CICAR), Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Sheng-Fan
authors.initials: SF
authors.lastname: Wang
authors.affiliation: Center for Infectious Disease and Cancer Research (CICAR), Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Lin
authors.affiliation: Center for Infectious Disease and Cancer Research (CICAR), Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Yen
authors.affiliation: Center for Infectious Disease and Cancer Research (CICAR), Kaohsiung Medical University, Kaohsiung, Taiwan; Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Taipei Veterans' General Hospital, Taipei, Taiwan.
authors.forename: Wing-Wai
authors.initials: WW
authors.lastname: Wong
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Kaohsiung Veterans' General Hospital, Kaohsiung, Taiwan.
authors.forename: Hung-Chin
authors.initials: HC
authors.lastname: Tsai
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
authors.forename: Chia-Jui
authors.initials: CJ
authors.lastname: Yang
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Taipei City Hospital, Taipei, Taiwan.
authors.forename: Bor-Shen
authors.initials: BS
authors.lastname: Hu
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Taichung Veterans' General Hospital, Taichung, Taiwan.
authors.forename: Yu-Huei
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chin-Tien
authors.initials: CT
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Children's Healthcare of Atlanta and Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Jaang-Jiun
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Zixin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
authors.affiliation: School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Yen-Hsu
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Center for Infectious Disease and Cancer Research (CICAR), Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Microbiology, Institute of Medical Research and Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yi-Ming Arthur
authors.initials: YM
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D015331:Cohort Studies; D018450:Disease Progression; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D019713:Receptors, CCR5 / Q000378:metabolism; D017384:Sequence Deletion; D013045:Species Specificity; D019562:Viral Load; D056189:Viral Tropism; D014779:Virus Replication; D055815:Young Adult; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics
chemical_list: C584933:CCR5 protein, human; D019713:Receptors, CCR5; D054301:gag Gene Products, Human Immunodeficiency Virus; C083002:p6 gag protein, Human immunodeficiency virus 1