Which NK cell populations mark the high burden of CMV present in all HIV patients beginning ART in Indonesia?

Abstract

Background: Cytomegalovirus (CMV) has been linked with cardiovascular disease (CVD) in populations where some individuals are seronegative. However, effects of CMV are unclear in HIV patients who all have high levels of CMV antibodies. Other metrics of their CMV burden are needed. Amongst transplant recipients, CMV drives the expansion of NK cell populations expressing NKG2C and/or LIR1 and lacking FcRγ. Methods: Indonesian HIV patients (n = 40) were tested before ART and after 6 months, with healthy local controls (n = 20). All patients had high CMV antibody titres. 52% started therapy with CMV DNA detectable by qPCR, providing a crude measure of CMV burden. Proportions of CD56Hi or CD56Lo NK cells expressing FcRγ, NKG2C or LIR1 were determined flow cytometrically. CVD was predicted using carotid intimal media thickness (cIMT). Values were correlated with levels of CMV antibodies on ART. Results: Patients had low proportions of CD56Lo and more CD56Hi NK cells. However proportions of FcRγ− NK cells were lowest in patients with CMV DNA, and cIMT values related inversely with FcRγ− NK cells in these patients. Percentages of NKG2C+CD56Lo NK cells were similar in patients and controls, but rose in patients with CMV DNA. Proportions of NKG2C+ CD56Hi NK cells correlated with levels of CMV antibodies in CMV DNA-negative patients. Conclusions: We show that the very high burdens of CMV in this population confound systems developed to study effects of CMV in other populations. FcRγ− NK cells may be depleted by very high CMV burdens, but NKG2C and antibody levels may be informative in patients on ART.