Chronic HIV-1 viremia reverses NKG2A/NKG2C ratio on natural killer cells in patients with human cytomegalovirus co-infection

Enrico Brunetta, Manuela Fogli, Stefania Varchetta, Luisa Bozzo, Kelly L. Hudspeth, Emanuela Marcenaro, Alessandro Moretta, Domenico Mavilio

Research output: Contribution to journalArticlepeer-review


Background: The HIV-1-induced expansion of highly dysfunctional natural killer (NK) cell subsets represents a strategy to evade NK cell antiviral functions. In this context, the loss of NKG2A NK cells in chronic viremic HIV-1-infected individuals has also been associated with a dramatic expansion of NKG2C NK cells. The viral trigger associated with high frequencies of NK cell subsets expressing NKG2C is still being debated. Objective: To confirm that human cytomegalovirus (HCMV) infection is necessary for the expansion of NKG2C NK cells and to assess whether this phenomenon affects NKG2A/NKG2C ratio on NK cells in patients coinfected with HIV-1 and HCMV. Design: We measured the expression of NKG2A and NKG2C on NK cells from 70 healthy donors, 21 early, 96 chronic and 27 long-term nonprogressor's (LTNPs) HIV-1-infected patients using a multicolor flow cytometric approach. HCMV infection was detected by titrating the serum levels of specific circulating antibodies. Results: A significant expansion of NKG2C NK cells could be detected only in HCMV-infected patients. This phenotypic feature, together with the HIV-1-mediated downmodulation of NKG2A, pathologically reverses the ratio of NKG2A/NKG2C uniquely on NK cells from chronic viremic HIV-1-infected patients with a concomitant HCMV infection. The normalization of NKG2A/NKG2C ratio to values more than one occurred only after 24 months of suppression of HIV-1 replication following antiretroviral therapy. Conclusion: The inversion of NKG2A/NKG2C ratio characterizes advanced stages of HIV-1 disease in patients showing a concomitant HCMV infection. This NK cell immune parameter renders this cohort of patients distinguishable from LTNPs and early HIV-1-infected individuals.

Original languageEnglish
Pages (from-to)27-34
Number of pages8
JournalAIDS (London, England)
Issue number1
Publication statusPublished - Jan 2010


  • Antiretroviral therapy
  • Biomarker
  • Human cytomegalovirus coinfection
  • Natural killer cell subsets
  • NKG2A/NKG2C ratio

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Infectious Diseases


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