The conserved carboxy terminal region of HIV-1 gp120 is recognized by seronegative HIV-exposed people

Brown, L. Neville; Souberbielle, Bernard; Marriott, J Blake; Westby, Mike; Desselberger, Ulrich; Kaye, T.; Gougeon, Marie‐Lise; Dalgleish, Angus

doi:10.1097/00002030-199912240-00004

Cited by 15 publications

(5 citation statements)

References 23 publications

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“…Increased HIV Env specific plasma IgG in HIV negative individuals has been previously reported, particularly in some individuals with frequent HIV exposure. 89 , 90 , 91 , 92 Though not statistically significant based on Approach 1, similar trends are seen across the three approaches. One potential explanation is that elevated baseline HIV-specific plasma IgG may also be the consequence of antibodies that are developed in response to microbiome exposure and cross-react with HIV Env and can further expand following HIV vaccination or HIV infection, as has been described for gp41.…”

Section: Discussionmentioning

confidence: 62%

Baseline host determinants of robust human HIV-1 vaccine-induced immune responses: A meta-analysis of 26 vaccine regimens

et al. 2022

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Section: Discussionmentioning

confidence: 62%

Baseline host determinants of robust human HIV-1 vaccine-induced immune responses: A meta-analysis of 26 vaccine regimens

et al. 2022

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“…The second schema, of relevance only for HIV, is that HIV proteins, in particular gp120, show particular homology to HLA proteins, likely due to shared affinity for binding to the host CD4 protein. Notable homologies between HIV and host proteins has been summarized in Supplementary Table 1 ( 31 , 43 – 51 ) including additional homologies reported between class 2 HLA and other HIV proteins including gp41 and Nef ( 45 , 52 – 54 ). HIV gp120 has even been shown to be able to present peptide as antigen, analogous to peptide presentation by class 2 HLA ( 41 , 55 ).…”

Section: Discussionmentioning

confidence: 99%

“…In highly HIV-exposed, persistently seronegative people, 30% had antibodies that reacted with gp120 and 70% had antibodies to class 1 HLA, leading the authors to hypothesize that antibodies against HLA might be protective against HIV acquisition ( 31 ). In persistently HIV seronegative intravenous drug users, antibodies against HLA (cross-reactive with HIV) were present in 33%, but in only 4% of healthy controls ( 32 ).…”

Section: Introductionmentioning

confidence: 99%

Alloimmunity to Class 2 Human Leucocyte Antigens May Reduce HIV-1 Acquisition – A Nested Case-Control Study in HIV-1 Serodiscordant Couples

et al. 2022

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Enveloped viruses, including the Human Immunodeficiency Virus-1 (HIV), incorporate host proteins such as human leucocyte antigens (HLA) into their envelope. Pre-existing antibodies against HLA, termed HLA antibodies, may bind to these surface proteins and reduce viral infectivity. Related evidence includes macaque studies which suggest that xenoimmunization with HLA antigens may protect against simian immunodeficiency virus infection. Since HIV gp120 shows homology with class 2 HLA, including shared affinity for binding to CD4, class 2 HLA antibodies may influence HIV acquisition via binding to gp120 on the viral envelope. We conducted a nested case-control study on HIV serodiscordant couples, comparing the frequency of HLA antibodies among highly exposed persistently seronegative controls with those who went on to acquire HIV (HIV-seroconverters). We first performed low resolution HLA typing on 143 individuals who were HIV-infected at enrollment (index partners) and their corresponding sexual partners (115 highly exposed persistently seronegative individuals and 28 HIV-seroconverters). We then measured HLA class 1 and 2 antibodies in the highly exposed persistently seronegative individuals and HIV-seroconverters at early and late timepoints. We analyzed whether such antibodies were directed at HLA specificities of their HIV-infected index partners, and whether autoantibodies or complement-fixing class 2 HLA antibodies were present. Seventy-nine percent of highly exposed persistently seronegative individuals had HLA antibodies; 56% against class 1 and 50% against class 2 alleles. Half of the group of highly exposed persistently seronegative individuals, prior to seroconversion, expressed class 2 HLA antibodies, compared with only 29% of controls (p=0.05). HIV infection was a sensitizing event leading to de novo development of antibodies against HLA-A and HLA-B loci, but not against class 2 loci. HLA autoantibodies were present in 27% of highly exposed persistently seronegative individuals. Complement-fixing class 2 HLA antibodies did not differ significantly between highly exposed persistently seronegative individuals and seroconverters. In multivariable regression, presence of class 2 HLA antibodies at early timepoints was associated with reduced odds of HIV acquisition (odds ratio 0.330, confidence interval 0.112-0.976, p=0.045). These epidemiological data suggest that pre-existing class 2 HLA antibodies were associated with reduced odds of HIV acquisition.

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“…31 Antibodies against the C5 region are also evident in patients who are heavily exposed but uninfected. 32 This thus raises the question of whether inducing responses to non-neutralising epitopes could reduce activation and progression to disease.…”

Section: Cd4mentioning

confidence: 99%

Pathogenesis of HIV: non-specific immune hyperactivity and its implications for vaccines

Cadogan

Dalgleish

2008

Clinical Medicine

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-More than a decade ago, the pathogenesis of AIDS was reviewed in this journal, using the subtitle 'classical and alternative views', when evidence was accumulating that HIV could not cause AIDS simply through direct cytopathic mechanisms alone. Generalised immune activation after infection with HIV is now understood to be associated with and predictive of disease progression and probably represents the single most important difference between rapid progression and slow or non-progression. However, the fundamental source of this phenomenon remains undetermined. Do pathogenic events after acute infection promote an environment susceptible to increased hyperactivity or does inherent reactivity towards HIV in susceptible individuals ultimately influence these processes? New strategies aimed at eliminating HIV-induced immune activation are required, as is investigation into the clinical and immunological influence of antibodies that target HIV epitopes associated with disease and that are not necessarily neutralising. Therapeutic vaccines to prevent disease may be more practical and effective than classic prophylactic vaccination.

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The conserved carboxy terminal region of HIV-1 gp120 is recognized by seronegative HIV-exposed people

Abstract: Our results suggest that antibody responses against the C-terminal region of HIV gp120 and HLA class I may represent markers of apparent natural protection against HIV-1 infection.

Cited by 15 publications

References 23 publications

Baseline host determinants of robust human HIV-1 vaccine-induced immune responses: A meta-analysis of 26 vaccine regimens

Baseline host determinants of robust human HIV-1 vaccine-induced immune responses: A meta-analysis of 26 vaccine regimens

Alloimmunity to Class 2 Human Leucocyte Antigens May Reduce HIV-1 Acquisition – A Nested Case-Control Study in HIV-1 Serodiscordant Couples

Pathogenesis of HIV: non-specific immune hyperactivity and its implications for vaccines

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