Chronic HIV-1 viremia reverses NKG2A/NKG2C ratio on natural killer cells in patients with human cytomegalovirus co-infection
E Brunetta, M Fogli, S Varchetta, L Bozzo, KL Hudspeth… - Aids, 2010 - journals.lww.com
Aids, 2010•journals.lww.com
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 pos NK cells in chronic viremic HIV-1-infected individuals has also been associated
with a dramatic expansion of NKG2C pos 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 …
subsets represents a strategy to evade NK cell antiviral functions. In this context, the loss of
NKG2A pos NK cells in chronic viremic HIV-1-infected individuals has also been associated
with a dramatic expansion of NKG2C pos 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 …
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 pos NK cells in chronic viremic HIV-1-infected individuals has also been associated with a dramatic expansion of NKG2C pos 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 pos 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 pos 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.
Lippincott Williams & Wilkins