Sequencing of the Viral UL111a Gene Directly from Clinical Specimens Reveals Variants of HCMV-Encoded IL-10 That Are Associated with Altered Immune Responses to HCMV

Abstract

Human cytomegalovirus (HCMV) is a beta-herpesvirus carried by ~80% of adults worldwide. Acute infections are often asymptomatic in healthy individuals but generate diverse syndromes in neonates, renal transplant recipients (RTR), and people with HIV (PWH). The HCMV gene UL111a encodes a homolog of human interleukin-10 (IL-10) that interacts with the human IL-10 receptor. Deep sequencing technologies were used to sequence UL111a directly from 59 clinical samples from Indonesian PWH and Australian RTR, healthy adults, and neonates. Overall, 93% of samples contained more than one variant of HCMV, as defined by at least one nonsynonymous variation. Carriage of these variants differed between neonates and adults, Australians and Indonesians, and between saliva and blood leukocytes. The variant alleles of N41D and S71Y occurred together in Australian RTR and were associated with higher T-cell responses to HCMV pp65. The variant P122S was associated with lower levels of antibodies reactive with a lysate of HCMV-infected fibroblasts. L174F was associated with increased levels of antibodies reactive with HCMV lysate, immediate-early 1 (IE-1), and glycoprotein B (gB) in Australian RTR and Indonesians PWH, suggesting a higher viral burden. We conclude that variants of UL111a are common in all populations and may influence systemic responses to HCMV.

Variants of HCMV UL18 Sequenced Directly from Clinical Specimens Associate with Antibody and T-Cell Responses to HCMV

“…In this study, we identify nonsynonymous variants in the UL18 gene by sequencing HCMV directly from clinical samples. Compared to our analyses of US28 and UL111a in the same samples [ 29 , 35 ], UL18 had a higher amount of variation. Several variations were donor group specific, but eight were present in all cohorts and all sample types.…”

Study of Cytokine Levels: Ifn-Γ, Il-29, Il-28b, TNF-Α, Il-10 in Blood Serum of Hiv-Positive Patients With Cytomegalovirus Infection

“…После первичного заражения иммунокомпетентного хозяина запускается реализация как врожденного, так и приобретенного иммунитета, механизмы которого блокируют репликацию ЦМВ. Однако ввиду вирусной эвазии геном ЦМВ сохраняется в виде эписомы в ядрах клеток хозяина, что приводит к бессимптомной, пожизненной инфекции, которая сохраняется в виде латентной формы [3,4,5].…”