Killer-cell immunoglobulin-like receptors associate with HIV-1 infection in a narrow-source Han Chinese cohort

Linghang Wang,Keyi Xu,Sarah Rowland-Jones,Yonghong Zhang,Louis-Marie Yindom,Tao Dong,William A Paxton

doi:10.1371/journal.pone.0195452

Abstract

BackgroundThe HIV pandemic remains the most serious challenge to public health worldwide. The hallmark characteristics of the disease is the eventual failure of the immune system to control opportunistic infections and death. However not everyone who has HIV develops the disease at the same rate and so we are studying how the immune system works to control the virus in those who have been infected for decades and remain relatively healthy without the need of anti-retroviral therapy (ART).MethodsGenomic DNA samples from 513 Chinese Han individuals from Henan province were typed for 15 KIR and 3 HLA class I genes. Genotype frequencies were compared between a village cohort of 261 former plasma donors (SM cohort) infected with HIV-1 through an illegal plasma donor scheme who survived more than 10 years of infection without ART and 252 ethnically-matched healthy controls from a nearby village. KIR and HLA were molecularly typed using a combination of polymerase chain reaction (PCR) with sequence-specific primers (PCR-SSP) and sequence based techniques.ResultsAll 15 KIR genes were observed in the study population at various frequencies. KIR2DL3 was significantly less common in the HIV-1 infected group (95.8% vs 99.2%, p = 0.021). The combination of KIR3DS1 with homozygosity for HLA-Bw4 alleles (the putative ligand for KIR3DS1) was significantly less frequent in the HIV-1 infected group than in the control group (6.0% vs 12.0% respectively, p = 0.023).ConclusionSpecific KIR-HLA compound genotypes associate with differential outcomes to infection and disease progression following exposure to a narrow-source HIV-1.

Highlights

Natural Killer (NK) cells play a bridging role between innate immunity and adaptive immunity to control viral infection and malignant diseases
Not everyone who has HIV develops the disease at the same rate and so we are studying how the immune system works to control the virus in those who have been infected for decades and remain relatively healthy without the need of anti-retroviral therapy (ART)
Genotype frequencies were compared between a village cohort of 261 former plasma donors (SM cohort) infected with HIV-1 through an illegal plasma donor scheme who survived more than 10 years of infection without ART and 252 ethnically-matched healthy controls from a nearby village

Summary

Introduction

Natural Killer (NK) cells play a bridging role between innate immunity and adaptive immunity to control viral infection and malignant diseases. Of all the NK cell receptors, KIRs are by far the most polymorphic and could explain differential responses to viral infections between individuals. The expression of KIRs on NK cells is stochastic and variegated [3,4]. All these levels of KIR variation can influence the host immune responses to infection. Not everyone who has HIV develops the disease at the same rate and so we are studying how the immune system works to control the virus in those who have been infected for decades and remain relatively healthy without the need of anti-retroviral therapy (ART)

Methods

Discussion

Conclusion