HLA-associated protection of lymphocytes during influenza virus infection

Eliana E Ochoa,Frank M Domurat,Norbert J Roberts,David J Mock,Joan E Nichols,Ruksana Huda,Nayef El-Daher,Steven F Scheibel

doi:10.1186/s12985-020-01406-x

Abstract

BackgroundHeterozygosity at HLA class I loci is generally considered beneficial for host defense. We report here an element of HLA class I homozygosity that may or may not help preserve its existence in populations but which could indicate a new avenue for antiviral research.MethodsLymphocytes from serologically HLA-homozygous or -heterozygous donors were examined for synthesis of influenza virus proteins and RNA after exposure to virus as peripheral blood mononuclear cells. The virus-exposed lymphocytes were also examined for internalization of the virus after exposure, and for susceptibility to virus-specific cytotoxic T lymphocytes in comparison with virus-exposed monocytes/macrophages and unseparated peripheral blood mononuclear cells. Results were compared using two-tailed Fisher’s exact test.ResultsSerologically-defined HLA-A2-homozygous lymphocytes, in contrast to heterozygous lymphocytes, did not synthesize detectable influenza virus RNA or protein after exposure to the virus. HLA-A2-homozygous lymphocytes, including both homozygous and heterozygous donors by genetic sequence subtyping, did internalize infectious virus but were not susceptible to lysis by autologous virus-specific cytotoxic T lymphocytes (“fratricide”). Similar intrinsic resistance to influenza virus infection was observed with HLA-A1- and HLA-A11-homozygous lymphocytes and with HLA-B-homozygous lymphocytes.ConclusionsA significant proportion of individuals within a population that is characterized by common expression of HLA class I alleles may possess lymphocytes that are not susceptible to influenza virus infection and thus to mutual virus-specific lysis. Further study may identify new approaches to limit influenza virus infection.

Highlights

Heterozygosity at HLA class I loci is generally considered beneficial for host defense
We report here a unique, and surprising, potentially protective element for human lymphocytes associated with HLA class I serological homozygosity that may suggest new antiviral approaches to influenza virus infection even if it does not help preserve and ensure the existence of HLA homozygosity in populations
The peripheral blood mononuclear cells (PBMC) were cultured at 37 °C in medium 199 (M199) with 10% heat-inactivated fetal calf serum (FCS) except during one-hour exposures to infectious influenza virus when they were suspended in serum-free medium [21, 22]

Summary

Introduction

Heterozygosity at HLA class I loci is generally considered beneficial for host defense. The current studies were undertaken in response to some surprising HLA-related results in studies of the requirement for monocyte/macrophage participation for influenza virus infection of human lymphocytes [15, 16]. Those studies showed that influenza virus infection of human lymphocytes occurs in the immune cell cluster of the developing antiviral response. We report here a unique, and surprising, potentially protective element for human lymphocytes associated with HLA class I serological homozygosity that may suggest new antiviral approaches to influenza virus infection even if it does not help preserve and ensure the existence of HLA homozygosity in populations

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Results

Discussion

Conclusion