Volume 22, No 5, May 2012

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 22 Issue 5, May 2012: 903-914

ORIGINAL ARTICLES

Preferential CTL targeting of Gag is associated with relative viral control in long-term surviving HIV-1 infected former plasma donors from China

Mingming Jia^1,*, Kunxue Hong^1,*, Jianping Chen¹, Yuhua Ruan¹, Zhe Wang², Bing Su³, Guoliang Ren¹, Xiaoqing Zhang¹, Zhen Liu¹, Quanbi Zhao¹,

¹State 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
²Henan Center for Disease Control and Prevention, Zhengzhou, Henan 450016, China
³Anhui Center for Disease Control and Prevention, Hefei, Anhui 230061, China
⁴Ragon Institute of MGH, MIT, and Harvard, Charlestown, MA 02129, USA Correspondence: Yiming Shao,(yshao08@gmail.com)

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.

Cell Research (2012) 22:903-914. doi:10.1038/cr.2012.19; published online 31 January 2012

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