HLA-associated protection of lymphocytes during influenza virus infection
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RESEARCH
Open Access
HLA-associated protection of lymphocytes during influenza virus infection Eliana E. Ochoa1, Ruksana Huda1, Steven F. Scheibel2, Joan E. Nichols1, David J. Mock2, Nayef El-Daher2, Frank M. Domurat2 and Norbert J. Roberts Jr1,2,3*
Abstract Background: Heterozygosity 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. Methods: Lymphocytes 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 virusexposed 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. Results: Serologically-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. Conclusions: A 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. Keywords: HLA, Human leukocyte antigen, Influenza virus, Human lymphocytes, Homozygosity, Monocytes/ macrophages
Background Heterozygosity at HLA class I loci is generally considered beneficial by assuring that individuals, and therefore the population, can respond to a wide variety of infectious challenges [1–3]. However, some alleles are so * Correspondence: [email protected] 1 Division of Infectious Diseases, Department of Internal Medicine and the Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA 2 Infectious Diseases Unit, University of Rochester School of Medicine, Rochester, NY, USA Full list of author information is available at the end of the article
common, for example HLA-A1 and -A2 in Caucasians [4–6], that a subpopulation of up to 4–5% would be homozygous by serological typing or, even in some populations for HLA-A2, by 6-digit high resolution sequence-based typing [7]. This might reflect selection due to recurrent or predominant infectious threats to the population [8
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