High polymorphism rates in well-known T cell epitopes restricted by protective HLA alleles during HIV infection are associated with rapid disease progression in early-infected MSM in China

He, Chuan; Han, Xiaoxu; Zhang, Hui; Jiang, Fanming; An, Minghui; Zhao, Bin; Ding, Haibo; Zhang, Zining; Dong, Tao; Shang, Hong

doi:10.1007/s00430-019-00585-x

Cited by 9 publications

(10 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The wide distribution of HLA alleles and the presence of differing epidemic HIV-1 strains among different populations lead to differing T-cell response characteristics [ 14 , 15 ]. Honeyborne and colleagues identified six different B*13-restricted T-cell epitopes in C subtype HIV-1-infected people in Durban, South Africa [ 19 ], while GI11 (Gag), VV9 (Gag), and RI9 (Gag) were identified as immunodominant epitopes, while Gag-specific T-cell responses were associated with the control of viremia [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…Several protective epitopes have been identified, including the human leukocyte antigen (HLA)-B*27-restricted KRWIILGLNK (Gag 263–272 , KK10) epitope [ 10 ]; the B*57-restricted TSTLQEQIAW (Gag 240–249 , TW10) epitope [ 11 , 12 ]; the B*51-restricted NANPDCKTI (Gag 327–345 , NI9) epitope [ 13 ]; and the B*13-restricted RQANFLGKI (Gag 429−437, RI9) and HQPISPRTL (Gag 144−152 , HL9) epitopes [ 14 ]. However, the many polymorphisms among the different HIV-1 subtypes [ 15 ] and immune-escape variants driven by T-cell responses [ 16 – 18 ] are major obstacles for immunogen screening. Consequently, understanding the kinetics of early protective immune responses to HIV-1 and the dynamics of escape mutations are extremely important for vaccine development.…”

Section: Introductionmentioning

confidence: 99%

“…The immunodominant epitopes and variation features driven by T-cell responses are reported to be HIV-1 subtype-specific due to sequence heterogeneity [ 15 ]. HLA-B*13 is associated with delayed disease progression in C subtype HIV-1-infected African populations and the features associated with B*13-restricted T-cell responses have been studied [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design

Zhang

Jiang

et al. 2022

BMC Immunol

Self Cite

View full text Add to dashboard Cite

Background Identifying immunogens which can elicit effective T cell responses against human immunodeficiency virus type 1 (HIV-1) is important for developing a T-cell based vaccine. It has been reported that human leukocyte antigen (HLA)-B*13-restricted T-cell responses contributed to HIV control in subtype B′ and C infected individuals. However, the kinetics of B*13-restricted T-cell responses, viral evolution within epitopes, and the impact on disease progression in CRF01_AE subtype HIV-1-infected men who have sex with men (MSM) are not known. Results Interferon-γ ELISPOT assays and deep sequencing of viral RNAs were done in 14 early HLA-B*13-positive CRF01_AE subtype HIV-1-infected MSM. We found that responses to RQEILDLWV (Nef106–114, RV9), GQMREPRGSDI (Gag226–236, GI11), GQDQWTYQI (Pol487–498, GI9), and VQNAQGQMV (Gag135–143, VV9) were dominant. A higher relative magnitude of Gag-specific T-cell responses, contributed to viral control, whereas Nef-specific T-cell responses were associated with rapid disease progression. GI11 (Gag) was conserved and strong GI11 (Gag)-specific T-cell responses showed cross-reactivity with a dominant variant, M228I, found in 3/12 patients; GI11 (Gag)-specific T-cell responses were positively associated with CD4 T-cell counts (R = 0.716, P = 0.046). Interestingly, the GI9 (Pol) epitope was also conserved, but GI9 (Pol)-specific T-cell responses did not influence disease progression (P > 0.05), while a D490G variant identified in one patient did not affect CD4 T-cell counts. All the other epitopes studied [VV9 (Gag), RQYDQILIEI (Pol113–122, RI10), HQSLSPRTL (Gag144–152, HL9), and RQANFLGRL (Gag429–437, RL9)] developed escape mutations within 1 year of infection, which may have contributed to overall disease progression. Intriguingly, we found early RV9 (Nef)-specific T-cell responses were associated with rapid disease progression, likely due to escape mutations. Conclusions Our study strongly suggested the inclusion of GI11 (Gag) and exclusion of RV9 (Nef) for T-cell-based vaccine design for B*13-positive CRF01_AE subtype HIV-1-infected MSM and high-risk individuals.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design

Zhang

Jiang

et al. 2022

BMC Immunol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Studies investigating SNPs in genetic regions of other interferon types and CXCL12 may help clarify this hypothesis 13 . Only large datasets, especially including HLA alleles with functional verification, can address this question 14‐16 . However, the exact mechanisms by which IFN λ 3 polymorphisms affect immune function or exert specific antiviral effects are still unclear 3,17 .…”

Section: Discussionmentioning

confidence: 99%

AIDS incidence and survival in a hospital‐based cohort of HIV‐positive patients from São Paulo, Brazil: The role of IFN‐λ4 polymorphisms

Prates

Malta

Gonçalves

et al. 2020

Journal of Medical Virology

View full text Add to dashboard Cite

Few studies have reported the prognosis of human immunodeficiency virus (HIV)‐positive patients followed for a long time in Brazil, particularly those including pre and post‐HAART eras. The polymorphisms of interferon (IFN)‐λ4 have been postulated as possibly associated with the pathogenesis of HIV infection. The aim of this study was to describe the incidence and mortality from a cohort of HIV‐positive patients as well as whether IFN‐λ4 gene polymorphisms (SNP rs8099917 and SNP rs12979860) were associated with HIV/acquired immune deficiency syndrome (AIDS) progression. We followed 402 patients for up to 30 years; 347 of them began follow‐up asymptomatic, without any AIDS‐defining opportunistic disease and/or a lymphocytes T CD4+ count of 350 cells/mm3 or lower. We determined the probability of the asymptomatic subjects to remain AIDS‐free, and the risk of death for those entering the study already with an AIDS diagnosis, as well as for subjects developing AIDS during follow‐up. We compared the prognosis of patients with two different polymorphisms for the genes encoding for IFN‐λ4, variants rs8099917 and rs12979860. The follow‐up time of the 347 asymptomatic‐at‐entry subjects was 3687 person‐years. IFN‐λ4 rs8099917 polymorphisms were not associated with AIDS progression, but IFN‐λ4 rs12979860 wild type genotype (CC) was associated with higher mortality compared to CT and TT, with an increased probability of death from AIDS (P = .01). In conclusion, genetic variations in IFN‐λ4 on rs12979860 polymorphisms in HIV‐infected patients may drive mortality risk.

show abstract

“…Patient LNA819 was recruited from a previously described (26)(27)(28)(29) large-scale, prospective, high-risk, MSM cohort in Liaoning Province, China. Briefly, HIV-1-negative MSM were followed up every 8 weeks.…”

Section: Study Participantmentioning

confidence: 99%

HIV-1–Specific Immunodominant T-Cell Responses Drive the Dynamics of HIV-1 Recombination Following Superinfection

et al. 2022

Self Cite

View full text Add to dashboard Cite

A series of HIV-1 CRF01_AE/CRF07_BC recombinants were previously found to have emerged gradually in a superinfected patient (patient LNA819). However, the extent to which T-cell responses influenced the development of these recombinants after superinfection is unclear. In this study, we undertook a recombination structure analysis of the gag, pol, and nef genes from longitudinal samples of patient LNA819. A total of 9 pol and 5 nef CRF01_AE/CRF07_BC recombinants were detected. The quasispecies makeup and the composition of the pol and nef gene recombinants changed continuously, suggestive of continuous evolution in vivo. T-cell responses targeting peptides of the primary strain and the recombination regions were screened. The results showed that Pol-LY10, Pol-RY9, and Nef-GL9 were the immunodominant epitopes. Pol-LY10 overlapped with the recombination breakpoints in multiple recombinants. For the LY10 epitope, escape from T-cell responses was mediated by both recombination with a CRF07_BC insertion carrying the T467E/T472V variants and T467N/T472V mutations originating in the CRF01_AE strain. In pol recombinants R8 and R9, the recombination breakpoints were located ~23 amino acids upstream of the RY9 epitope. The appearance of new recombination breakpoints harboring a CRF07_BC insertion carrying a R984K variant was associated with escape from RY9-specific T-cell responses. Although the Nef-GL9 epitope was located either within or 10~11 amino acids downstream of the recombination breakpoints, no variant of this epitope was observed in the nef recombinants. Instead, a F85V mutation originating in the CRF01_AE strain was the main immune escape mechanism. Understanding the cellular immune pressure on recombination is critical for monitoring the new circulating recombinant forms of HIV and designing epitope-based vaccines. Vaccines targeting antigens that are less likely to escape immune pressure by recombination and/or mutation are likely to be of benefit to patients with HIV-1.

show abstract

High polymorphism rates in well-known T cell epitopes restricted by protective HLA alleles during HIV infection are associated with rapid disease progression in early-infected MSM in China

Cited by 9 publications

References 69 publications

A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design

A longitudinal analysis of immune escapes from HLA-B*13-restricted T-cell responses at early stage of CRF01_AE subtype HIV-1 infection and implications for vaccine design

AIDS incidence and survival in a hospital‐based cohort of HIV‐positive patients from São Paulo, Brazil: The role of IFN‐λ4 polymorphisms

HIV-1–Specific Immunodominant T-Cell Responses Drive the Dynamics of HIV-1 Recombination Following Superinfection

Contact Info

Product

Resources

About