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Simian Immunodeficiency Virus Infection Modulates CD94+ (KLRD1+) NK Cells in Rhesus Macaques.

Publication ,  Journal Article
Ram, DR; Lucar, O; Hueber, B; Reeves, RK
Published in: J Virol
August 15, 2019

Recently, we and others have shown that natural killer (NK) cells exhibit memory-like recall responses against cytomegalovirus (CMV) and human immunodeficiency/virus simian immunodeficiency virus (HIV/SIV) infections. Although the mechanism(s) have not been fully delineated, several groups have shown that the activating receptor NKG2C is elevated on NK cells in the context of rhesus CMV (rhCMV) or human CMV (hCMV) infections. CD94, which heterodimerizes with NKG2C is also linked to adaptive NK cell responses. Because nonhuman primates (NHP) play a crucial role in modeling HIV (SIV) infections, it is crucial to be able to assess and characterize the NKG2 family in NHP. Unfortunately, it is not possible to detect CD94 using commercially available antibodies in NHP. Our work, a first for NHP, has focused on developing RNA flow cytometry using mRNA transcripts as proxies distinguishing NKG2C from NKG2A. We have expanded the application of this technology and here we show the first characterization of CD94+ (KLRD1+) NK cells in NHP using multiparametric RNA flow cytometry. Peripheral blood mononuclear cells from naive and matched acutely (n = 4) or chronically (n = 12) SIV-infected rhesus macaques were analyzed by flow cytometry using commercially available antibodies, determining expression of transcripts for NKG2A, NKG2C, and CD94 (KLRC1, KLRC2, and KLRD1, respectively) on NK cells using RNA flow cytometry. Our data show that KLRC1+/- KLRC2+ KLRD1+ NK cells decrease following chronic, but not acute, infection with SIV. This approach will allow us to investigate the kinetics of infection and NK memory formation and will further improve our understanding of basic NK cell biology, especially in the context of SIV infection.IMPORTANCE Nonhuman primates play a crucial role in approximating human biology and many diseases that are difficult, if not impossible, to achieve in other animal models, notably HIV. Current advances in adaptive NK cell research positions us to address fundamental deficiencies in our fight against infection and disease at the earliest moments after infection or substantially earlier in disease progression. We show here that we can identify specific NK cell subpopulations that are modulated following chronic, but not acute, SIV infection. The ability to identify these subsets more precisely will inform therapeutic and vaccine strategies targeting an optimized NK cell response.

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Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

August 15, 2019

Volume

93

Issue

16

Location

United States

Related Subject Headings

  • Virology
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • NK Cell Lectin-Like Receptor Subfamily D
  • NK Cell Lectin-Like Receptor Subfamily C
  • Macaca mulatta
  • Lymphocyte Subsets
  • Killer Cells, Natural
  • Immunophenotyping
 

Citation

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Ram, D. R., Lucar, O., Hueber, B., & Reeves, R. K. (2019). Simian Immunodeficiency Virus Infection Modulates CD94+ (KLRD1+) NK Cells in Rhesus Macaques. J Virol, 93(16). https://doi.org/10.1128/JVI.00731-19
Ram, Daniel R., Olivier Lucar, Brady Hueber, and R Keith Reeves. “Simian Immunodeficiency Virus Infection Modulates CD94+ (KLRD1+) NK Cells in Rhesus Macaques.J Virol 93, no. 16 (August 15, 2019). https://doi.org/10.1128/JVI.00731-19.
Ram DR, Lucar O, Hueber B, Reeves RK. Simian Immunodeficiency Virus Infection Modulates CD94+ (KLRD1+) NK Cells in Rhesus Macaques. J Virol. 2019 Aug 15;93(16).
Ram, Daniel R., et al. “Simian Immunodeficiency Virus Infection Modulates CD94+ (KLRD1+) NK Cells in Rhesus Macaques.J Virol, vol. 93, no. 16, Aug. 2019. Pubmed, doi:10.1128/JVI.00731-19.
Ram DR, Lucar O, Hueber B, Reeves RK. Simian Immunodeficiency Virus Infection Modulates CD94+ (KLRD1+) NK Cells in Rhesus Macaques. J Virol. 2019 Aug 15;93(16).

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

August 15, 2019

Volume

93

Issue

16

Location

United States

Related Subject Headings

  • Virology
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • NK Cell Lectin-Like Receptor Subfamily D
  • NK Cell Lectin-Like Receptor Subfamily C
  • Macaca mulatta
  • Lymphocyte Subsets
  • Killer Cells, Natural
  • Immunophenotyping