title: Chronic HIV-1 viremia reverses NKG2A/NKG2C ratio on natural killer cells in patients with human cytomegalovirus co-infection.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory Clinical and Experimental Immunology, IRCCS, Istituto Clinico Humanitas, Rozzano, Milano, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Brunetta
authors.forename: Manuela
authors.initials: M
authors.lastname: Fogli
authors.forename: Stefania
authors.initials: S
authors.lastname: Varchetta
authors.forename: Luisa
authors.initials: L
authors.lastname: Bozzo
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Hudspeth
authors.forename: Emanuela
authors.initials: E
authors.lastname: Marcenaro
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.forename: Domenico
authors.initials: D
authors.lastname: Mavilio
mesh_terms: D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D015967:Gene Expression Regulation, Viral / Q000276:immunology*; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology / Q000821:virology; D008297:Male; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000097:blood / Q000276:immunology; D014766:Viremia / Q000276:immunology* / Q000821:virology
chemical_list: C527059:KLRC2 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C