Lynn M. Butler, Ph.D., from the Karolinska Institute in Stockholm, and colleagues examined kidney biopsies from CKD patients to determine if CMV was present. A mouse model was also examined to identify the effects of murine CMV infection.
The researchers found that kidneys from nine of 13 patients with CKD were positive for CMV protein and that blood levels of CMV immunoglobulin G inversely correlated with red blood cell count in these patients.
Systemic murine CMV infection decreased serum erythropoietin levels in mice. Human CMV inhibited hypoxia-induced expression of erythropoietin messenger RNA (mRNA) and protein in erythropoietin-producing cells.
This was mediated by CMV early gene expression, because ultraviolet-inactivated virus had no effect. Also, valganciclovir treatment showed that late gene expression was nonessential. Human CMV also inhibited constitutive production of hypoxia inducible factors (HIF)2α mRNA.
Nuclear accumulation of HIF2α was inhibited in CMV-infected cells, and the extent of inhibition correlated with CMV protein expression, based on single cell analysis.
“Our findings suggest that renal CMV infection could induce or exacerbate anemia in patients,” the authors write.