Effect of Fc Receptor Genetic Diversity on HIV-1 Disease Pathogenesis

Geraghty, Daniel E.; Thorball, Christian W.; Fellay, Jacques; Thomas, Rasmi

doi:10.3389/fimmu.2019.00970

Cited by 10 publications

(12 citation statements)

References 78 publications

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“…The copyright holder for this preprint (which this version posted May 15, 2021. ; https://doi.org/10.1101/2021.05.12.443737 doi: bioRxiv preprint study and may potentially be manipulated to improve vaccine efficacy (Chung & Alter, 2017;Geraghty, Thorball, Fellay, & Thomas, 2019;Tay, Wiehe, et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as the primary mechanism of vaccine-induced protection against HIV-1

Shangguan

Ehrenberg

Geretz

et al. 2021

Preprint

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A gene signature previously correlated with mosaic adenovirus 26 vaccine protection in simian immunodeficiency virus (SIV) and SHIV challenge models in non-human primates (NHP). In this report we investigated presence of this signature as a correlate of reduced risk in human clinical trials and potential mechanism for protection. The absence of this gene signature in the DNA/rAd5 human vaccine trial which did not show efficacy, strengthens our hypothesis that this signature is only enriched in studies that demonstrated protection. This gene signature was enriched in the partially effective RV144 human trial that administered the ALVAC/protein vaccine, and we find that the signature associates with both decreased risk of HIV-1 acquisition and increased vaccine efficacy. Total RNA-seq in a clinical trial that used the same vaccine regimen as the RV144 HIV vaccine implicated antibody-dependent cellular phagocytosis (ADCP) as a potential mechanism of vaccine protection. CITE-seq profiling of 53 surface markers and transcriptomes of 53,777 single cells from the same trial, showed that genes in this signature were primarily expressed in cells belonging to the myeloid lineage including monocytes, which are major effector cells for ADCP. The consistent association of this transcriptome signature with vaccine efficacy represents a tool both to identify potential mechanisms, as with ADCP here, and to screen novel approaches to accelerate development of new vaccine candidates.

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Section: Discussionmentioning

confidence: 99%

Monocyte-derived transcriptome signature indicates antibody-dependent cellular phagocytosis as the primary mechanism of vaccine-induced protection against HIV-1

Shangguan

Ehrenberg

Geretz

et al. 2021

Preprint

Self Cite

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“…Similarly, in a sub-analysis of 467 long-term non-progressors and 517 rapid progressors, there was no association between FcγRIIa polymorphisms and HIV-1 disease progression. Finally, in the same meta-analysis, FcγRIIIa polymorphisms were not associated with HIV-1 disease progression in the Swiss HIV Cohort Study (SHCS) ( 56 ). Although another study found homozygous FcγRIIIa-176V/V to be highly prevalent in HIV progressors on ART compared to untreated natural viral suppressors, they could not conclude on this polymorphism’s association with viral set point ( 47 ).…”

Section: Fcγr Polymorphisms Hiv Disease Progression and Art Outcomesmentioning

confidence: 96%

“…for viral clearance (63,64). When Geraghty et al examined the role of FcgRIIa-(rs1801274) and FcgRIIIa-(rs396991) polymorphisms in 6300 HIV+ adults with European ancestry from a previous GWAS (65), they did not find any association between these polymorphisms and HIV acquisition (56). Furthermore, in the largest study of its kind in Africa, Connolly and colleagues also found no association between FcgRIIa-H131R (rs1801274) and FcgRIIIa-V176F (rs396991) variants and HIV infection or CD4+ T-cell decline in two cohorts in Rwanda and Zambia (50).…”

Section: Fcgr Polymorphisms and The Risk Of Hiv-1 Infection With And Without Vaccinesmentioning

confidence: 99%

“…Studies have not provided conclusive data on the association between FcγR polymorphisms and HIV-1 infection ( 56 ). For instance, contrasting results were reported when FcγRIIa and FcγRIIIa were examined with the risk of perinatal HIV-1 infection among infants in Kenya ( 35 , 48 ).…”

Section: Fcγr Polymorphisms and The Risk Of Hiv-1 Infection With And Without Vaccinesmentioning

confidence: 99%

“…In a meta-analysis of several genome-wide association studies comprising 7,266 patients in the International Collaboration for the Genomics of HIV (ICGH), no association between FcγRIIa (rs1801274) and FcγRIIIa (rs396991) polymorphisms and viral set point was found [reviewed in ( 56 )]. Similarly, in a sub-analysis of 467 long-term non-progressors and 517 rapid progressors, there was no association between FcγRIIa polymorphisms and HIV-1 disease progression.…”

Section: Fcγr Polymorphisms Hiv Disease Progression and Art Outcomesmentioning

confidence: 99%

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Are Fc Gamma Receptor Polymorphisms Important in HIV-1 Infection Outcomes and Latent Reservoir Size?

et al. 2021

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Fc gamma receptors (FcγR) are cell surface glycoproteins which trigger specific effector-cell responses when cross-linked with the Fc portions of immunoglobulin (IgG) antibodies. During HIV-1 infection, the course of disease progression, ART response, and viral reservoir size vary in different individuals. Several factors may account for these differences; however, Fc gamma receptor gene polymorphisms, which influence receptor binding to IgG antibodies, are likely to play a key role. FcγRIIa (CD32) was recently reported as a potential marker for latent HIV reservoir, however, this assertion is still inconclusive. Whether FcγR polymorphisms influence the size of the viral reservoir, remains an important question in HIV cure studies. In addition, potential cure or viral suppression methods such as broadly neutralizing antibody (bNAbs) may depend on FcγRs to control the virus. Here, we discuss the current evidence on the potential role played by FcγR polymorphisms in HIV-1 infection, treatment and vaccine trial outcomes. Importantly, we highlight contrasting findings that may be due to multiple factors and the relatively limited data from African populations. We recommend further studies especially in sub-Saharan Africa to confirm the role of FcγRIIa in the establishment of latent reservoir and to determine their influence in therapies involving bNAbs.

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