Killer immunoglobulin-like receptor (KIR) genes are associated with the risk of episodes of high-level and detectable viremia among HIV controllers [version 1; peer review: 2 not approved]

Killer immunoglobulin-like receptor (KIR) genes are associated with the risk of episodes of high-level and detectable viremia among HIV controllers [version 1; peer review: 2 not approved]

Background: HIV controllers (HICs) constitute a heterogeneous group of HIV-1 individuals able to suppress plasma viremia to low or undetectable levels in the absence of antiretroviral therapy. Host genetic factors may be involved in the sustained control of viral replication observed. We investigate...

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Bibliographic Details
Published in:F1000 research Vol. 10; p. 546
Main Authors: De Sá, Nathalia Beatriz Ramos, Silva, Karina dos S, Ribeiro-Alves, Marcelo, Caetano, Diogo Gama, Côrtes, Fernanda Heloise, de Azevedo, Suwellen S. D, Hoagland, Brenda, Grinsztejn, Beatriz, Veloso, Valdilea G, Morgado, Mariza G, Teixeira, Sylvia Lopes Maia
Format: Journal Article
Language:English
Published: 2021
Subjects:
CCR5 Δ32
viral load
HLA
KIR
Inflammasome SNPs
HIV controllers
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Summary:Background: HIV controllers (HICs) constitute a heterogeneous group of HIV-1 individuals able to suppress plasma viremia to low or undetectable levels in the absence of antiretroviral therapy. Host genetic factors may be involved in the sustained control of viral replication observed. We investigated the distribution and the potential impact of human leukocyte antigens (HLA)-B and -C alleles, killer immunoglobulin-like receptor (KIR) genes, single nucleotide polymorphisms (SNPs) of the NLRP3, CARD8 and IL-1β inflammasome genes, and CCR5Δ32 mutation on the viral control among HICs. Methods: In total, 28 HICs were categorized as persistent elite controllers (PECs, n = 7), ebbing elite controllers (EECs, n = 7), and viremic controllers (VCs, n = 14) according to the level of natural suppression of viremia. HLA alleles were assigned by sequencing-based typing, KIR alleles by polymerase chain reaction (PCR) sequence-specific amplification, SNPs by real-time PCR, and the CCR5Δ32 mutation by PCR. Results: Significant differences were observed in the pairwise comparisons of protective HLA-B alleles, KIR Bx genotype, KIR2DL3 + C1 pair, KIR2DL5, and KIR2DS5 allelic carrier frequencies among the HIC groups. Multivariate models showed that HICs without the KIR2DL3 allele or without KIR2DL3 + C1/C2 pair, with the HLA-C*08 allele or with the NLRP3 rs10754558-G SNP had a higher mean hazard of a viral load above 2,000 copies/mL, while a lower mean hazard of this event was observed for HICs with KIR2DL5, KIR2DS1, KIR2DS5, and KIR3DS1 alleles. Moreover, HICs with the KIR2DS5 allele had less risk of undergoing viral load (VL) blips within the same normalized period than those participants without this allele, while HICs without the KIR2DL3 allele had a mean higher risk of experiencing VL blips. Conclusions: These results indicate that innate immune mechanisms may play an essential role in modulating the sustained control of viral replication in HICs.
ISSN:2046-1402
2046-1402
DOI:10.12688/f1000research.53683.1