Human immunodeficiency virus type 1 specific cytotoxic T lymphocyte responses in Chinese infected with HIV-1 B'/C Recombinant (CRF07_BC)

Chen, Jianping; Hong, Kui; Jia, Mingming; Liu, Hongwei; Zhang, Yuanzhi; Li, Sha; Zhang, Xiaoqing; Zhao, Hongjing; Peng, Hong; Ma, Ping; Xing, Hui; Ruan, Yuhua; Williams, Katie; Yu, Xu G.; Altfeld, Marcus; Walker, Bruce D.; Shao, Yiming

doi:10.1186/1742-4690-4-62

Cited by 7 publications

(6 citation statements)

References 50 publications

(82 reference statements)

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“…Additionally, in these studies (18,22,28) and our study, concordant and discordant responses are found. This phenomenon can be explained by (i) amino acid substitutions within the optimal epitope, (ii) substitutions in close proximity to the optimal epitope, and (iii) the relative position of the optimal epitope within a given peptide (peptide offsetting).…”

Section: Discussionsupporting

confidence: 74%

“…Initial reports included only subtype B-or C-infected patients (1,(47)(48)(49), but more recently other subtypes and CRF recombinant forms are being studied (18,22,27,28,35). On the other hand, the immunoprotective role of HIV-specific vaccine-induced T cells may be limited by the large genetic distance between viral strains circulating in different locations and the vaccine strain.…”

Section: Discussionmentioning

confidence: 99%

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Magnitude, Breadth, and Functional Profile of T-Cell Responses during Human Immunodeficiency Virus Primary Infection with B and BF Viral Variants

Turk

Gherardi

Laufer

et al. 2008

J Virol

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Human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocytes (CTLs) arising during the acute phase of infection are associated with containment of viral replication and resolution of acute-phase symptoms (5,13,14,44). Detailed characterization of these cell populations and viral immunodominant epitopes will provide key data for developing and enhancing immunization strategies. In this sense, one major challenge is HIV variability, characterized by substantial inter-and intraclade sequence diversity. To date, most reports aimed at studying CTL responses are focused on HIV clade Band C-infected patients. In Argentina, epidemiological studies revealed that early predominance of B subtype has been overshadowed by the emergence of BF recombinants (16,23,32,33,53). These reports indicate that near 50% of the HIVinfected people living in Argentina are infected either with the circulating recombinant form CRF12_BF or other BF recombinant forms related to CRF12_BF. Moreover, in other South American countries, such as Brazil and Uruguay, high prevalence of F subtype and BF recombinant variants are also found (16,32,34). These findings provide an adequate scenario to fill the gap concerning fine mapping of CTL responses in nonclade B-and C-infected patients.Cross-clade CTL responses were studied by different groups using different approaches. The first publications used vaccinia virus-based constructs or peptide pools as stimulating factors (2,19,20,27). Not until recently was fine mapping of these responses achieved by using individual peptides based on different subtypes (22,28). The latter allows for a more detailed and comprehensive understanding of cross-clade reactive populations.Here, cross-clade and clade-specific T-cell responses in Band BF-infected patients from Argentina are reported. These assays were performed shortly after seroconversion in order to avoid the confounders associated with viral diversification, selection of escape mutants, and superinfection. Overlapping peptides spanning the Nef protein were chosen as antigens because of the following: (i) Nef is halfway along the spectrum of variability found in HIV proteins; (ii) during primary HIV infection, Nef-specific CTLs represent between 46% and 94% of the total magnitude of the HIV T-cell response (43); (iii) Nef has, together with Gag, the highest epitope density (1,39). This study also contributes to minimizing the problem of breadth underestimation during CTL screening and provides insights into discrepancies of CD8 T-cell effector function.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Magnitude, Breadth, and Functional Profile of T-Cell Responses during Human Immunodeficiency Virus Primary Infection with B and BF Viral Variants

Turk

Gherardi

Laufer

et al. 2008

J Virol

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“…CTLs recognize fragments of viral proteins (CD8 epitopes) that are presented by HLA on the infected cell surface and subsequently kill the infected cell. Numerous studies have observed that CTLs frequently target CD8 epitopes in Vif (92)(93)(94)(95)(96)(97)(98). The pleiotropic effects of CTL-induced escape mutations that prevent viral recognition and the killing of infected cells depend on the affected Vif region and may destabilize the interactions between Vif and APOBEC3F, APOBEC3G, and/or other deaminases or the interactions between Vif and Elongin C. The importance of the specific Vif sequence in determining the biological outcome of the interaction between Vif and a range of APOBEC3 proteins is emphasized by reports demonstrating that, e.g., APOBEC3C and APOBEC3B are neutralized by some Vif variants but not others (40) and that Vif subtype variability affects the efficiency of the interaction with APOBEC3G (99).…”

Section: Figmentioning

confidence: 99%

Possible Footprints of APOBEC3F and/or Other APOBEC3 Deaminases, but Not APOBEC3G, on HIV-1 from Patients with Acute/Early and Chronic Infections

Armitage

Deforche

Welch

et al. 2014

J Virol

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Members of the apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like-3 (APOBEC3) innate cellular cytidine deaminase family, particularly APOBEC3F and APOBEC3G, can cause extensive and lethal G-to-A mutations in HIV-1 plusstrand DNA (termed hypermutation). It is unclear if APOBEC3-induced mutations in vivo are always lethal or can occur at sublethal levels that increase HIV-1 diversification and viral adaptation to the host. The viral accessory protein Vif counteracts APOBEC3 activity by binding to APOBEC3 and promoting proteasome degradation; however, the efficiency of this interaction varies, since a range of hypermutation frequencies are observed in HIV-1 patient DNA. Therefore, we examined "footprints" of APOBEC3G and APOBEC3F activity in longitudinal HIV-1 RNA pol sequences from approximately 3,000 chronically infected patients by determining whether G-to-A mutations occurred in motifs that were favored or disfavored by these deaminases. Gto-A mutations were more frequent in APOBEC3G-disfavored than in APOBEC3G-favored contexts. In contrast, mutations in APOBEC3F-disfavored contexts were relatively rare, whereas mutations in contexts favoring APOBEC3F (and possibly other deaminases) occurred 16% more often than average G-to-A mutations. These results were supported by analyses of >500 HIV-1 env sequences from acute/early infection. IMPORTANCECollectively, our results suggest that APOBEC3G-induced mutagenesis is lethal to HIV-1, whereas mutagenesis caused by APOBEC3F and/or other deaminases may result in sublethal mutations that might facilitate viral diversification. Therefore, Vifspecific cytotoxic T lymphocyte (CTL) responses and drugs that manipulate the interplay between Vif and APOBEC3 may have beneficial or detrimental clinical effects depending on how they affect the binding of Vif to various members of the APOBEC3 family.

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“…Median CD4 counts and plasma viral loads at the time of sampling were 378 cells/mm 3 (full range: 50–940 cells/mm 3 ) and 20,700 copies/ml (full range: <50–714,000 copies/ml), respectively (Table S1). Subjects became infected through sharing contaminated needles during drug use, and subjects were confirmed to be infected with CRF07_BC strain162526 (Table S1). The historical neutralization data of 103 subjects from the FPD cohort15 with over ten years’ infection time were used to compare with those generated in the IDU cohort.…”

Section: Methodsmentioning

confidence: 99%

“…Our laboratory previously studied the biological and virological characteristics25 and cytotoxic T lymphocyte (CTL) response pattern26 of CRF07_BC infection. However, the humoral response pattern during infection caused by this unique recombinant subtype has not yet been adequately investigated.…”

mentioning

confidence: 99%

Profiling the neutralizing antibody response in chronically HIV-1 CRF07_BC-infected intravenous drug users naïve to antiretroviral therapy

Zhao

et al. 2017

Sci Rep

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Characterizing neutralizing antibody (NAb) responses in individuals infected with diverse HIV-1 strains is necessary to reveal the novel targets for regional preventive and therapeutic strategies development. We evaluated the prevalence, breadth, and potency of NAb responses in 98 CRF07_BC-infected individuals using a large, multi-subtype panel of 30 tier 2-3 Env-pseudotyped viruses. Furthermore, we compared the neutralization pattern of CRF07_BC-infected people with that of subtype B’-infected individuals in China. Of the 98 plasma samples tested, 18% neutralized more than 80% of viruses in the panel, and 53% neutralized more than 50%, suggesting the presence of broadly NAbs in these individuals. A preferential intra-subtype neutralization of CRF07_BC was found. Notably, CRF07_BC-infected individuals generated higher neutralization titers against intra-subtype viruses than subtype B’-infected individuals with longer infection length. However, subtype B’-infected individuals mounted broader neutralization responses against inter-subtype viruses than CRF07_BC infection with shorter infection time, indicating the transition from narrow autologous to broad heterologous neutralization over time. Neutralization activity of the top six plasmas from each cohort was attributable to IgG fraction, and half of them developed CD4 binding site antibody reactivity. Heatmap analysis identified three statistically robust clusters of plasmas that offer valuable resources for further in-depth virological and immunological study.

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Human immunodeficiency virus type 1 specific cytotoxic T lymphocyte responses in Chinese infected with HIV-1 B'/C Recombinant (CRF07_BC)

Cited by 7 publications

References 50 publications

Magnitude, Breadth, and Functional Profile of T-Cell Responses during Human Immunodeficiency Virus Primary Infection with B and BF Viral Variants

Magnitude, Breadth, and Functional Profile of T-Cell Responses during Human Immunodeficiency Virus Primary Infection with B and BF Viral Variants

Possible Footprints of APOBEC3F and/or Other APOBEC3 Deaminases, but Not APOBEC3G, on HIV-1 from Patients with Acute/Early and Chronic Infections

Profiling the neutralizing antibody response in chronically HIV-1 CRF07_BC-infected intravenous drug users naïve to antiretroviral therapy

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