HLA-associated protection of lymphocytes during influenza virus infection
| Autor: | Steven F. Scheibel, Nayef El-Daher, Joan E. Nichols, Frank M. Domurat, Norbert J. Roberts, Eliana E. Ochoa, David J. Mock, Ruksana Huda |
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| Rok vydání: | 2020 |
| Předmět: |
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0301 basic medicine viruses Population Genes MHC Class I Human leukocyte antigen Biology Peripheral blood mononuclear cell Homozygosity Virus lcsh:Infectious and parasitic diseases HLA-A11 Antigen Loss of heterozygosity 03 medical and health sciences 0302 clinical medicine Human lymphocytes Virology HLA-A2 Antigen Influenza Human Humans Cytotoxic T cell lcsh:RC109-216 Allele education Alleles HLA-A1 Antigen education.field_of_study Macrophages Research Homozygote RNA HLA 030104 developmental biology Infectious Diseases Monocytes/macrophages Leukocytes Mononuclear Female 030211 gastroenterology & hepatology Influenza virus T-Lymphocytes Cytotoxic |
| Zdroj: | Virology Journal Virology Journal, Vol 17, Iss 1, Pp 1-13 (2020) |
| ISSN: | 1743-422X |
| DOI: | 10.1186/s12985-020-01406-x |
| Popis: | 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 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. 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. |
| Databáze: | OpenAIRE |
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