title: Preferential CTL targeting of Gag is associated with relative viral control in long-term surviving HIV-1 infected former plasma donors from China.
abstract: It is generally believed that CD8(+) cytotoxic T lymphocytes (CTLs) play a critical role in limiting the replication of human immunodeficiency virus type 1 (HIV-1) and in determining the outcome of the infection, and this effect may partly depend on which HIV product is preferentially targeted. To address the correlation between HIV-1-specific CTL responses and virus replication in a cohort of former plasma donors (FPDs), 143 antiretroviral therapy naive FPDs infected with HIV-1 clade B' strains were assessed for HIV-1-specific CTL responses with an IFN-γ Elispot assay at single peptide level by using overlapping peptides (OLPs) covering the whole consensus clade B proteome. By using a Spearman's rank correlation analysis, we found that the proportion of Gag-specific CTL responses among the total virus-specific CTL activity was inversely correlated with viral loads while being positively correlated to CD4 counts, as opposed to Pol- and Env-specific responses that were associated with increased viral loads and decreased CD4 counts. In addition, Vpr-specifc CTL responses showed a similar protective effect with Gag responses, but with a much lower frequency of recognition. Significantly, we also observed an association between HLA-A*30/B*13/Cw*06 haplotype and lower viral loads that was probably due to restricted Gag-specific CTL responses. Thus, our data demonstrate the prominent role of Gag-specific CTL responses in disease control. The advantage of HLA-A*30/B*13/Cw*06 haplotype in viral control may be associated with the contribution of Gag-specific CTL responses in the studied individuals.
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Jia
authors.forename: Kunxue
authors.initials: K
authors.lastname: Hong
authors.forename: Jianping
authors.initials: J
authors.lastname: Chen
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Ruan
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: Su
authors.forename: Guoliang
authors.initials: G
authors.lastname: Ren
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Quanbi
authors.initials: Q
authors.lastname: Zhao
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Peng
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Xu G
authors.initials: XG
authors.lastname: Yu
authors.forename: Yiming
authors.initials: Y
authors.lastname: Shao
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000627:therapeutic use; D001782:Blood Donors; D018791:CD4 Lymphocyte Count; D002681:China; D015331:Cohort Studies; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000378:metabolism*; D015234:HLA-A Antigens / Q000276:immunology; D059908:HLA-B13 Antigen / Q000276:immunology; D015236:HLA-C Antigens / Q000276:immunology; D006239:Haplotypes; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D015234:HLA-A Antigens; C069526:HLA-A*30 antigen; C519589:HLA-B*13:14 antigen; D059908:HLA-B13 Antigen; D015236:HLA-C Antigens; C528994:HLA-C*06 antigen; D010455:Peptides; D054301:gag Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma