Key result
HCMV UL18 variants linked to altered antibody and T-cell responses in HIV and transplant recipients.
Observational (n=60)
Yes
HCMV UL18 is a highly variable gene, and specific variants are associated with altered host immune responses and viral burden.
UL18 variants may influence HCMV immunity in HIV and transplant patients; hypothesis-generating for risk stratification, pending prospective validation.
Around 80% of adults worldwide carry human cytomegaloviris (HCMV). The HCMV gene UL18 is a homolog of HLA class I genes and encodes a protein with high affinity for the NK and T-cell cytotoxicity inhibitor LIR-1. UL18 was deep sequenced from blood, saliva or urine from Indonesian people with HIV (PWH) (n = 28), Australian renal transplant recipients (RTR) (n = 21), healthy adults (n = 7) and neonates (n = 4). 95% of samples contained more than one variant of HCMV UL18, as defined by carriage of nonsynonymous variations. When aligned with immunological markers of the host’s burden of HCMV, the S318N variation associated with high levels of antibody reactive with HCMV lysate in PWH over 12 months on antiretroviral therapy. The A107T variation associated with HCMV antibody levels and inflammatory biomarkers in PWH at early timepoints. Variants D32G, D248N, V250A and E252D aligned with elevated HCMV antibody levels in RTR, while M191K, E196Q and F165L were associated with HCMV-reactive T-cells and proportions of Vδ2− γδ T-cells—populations linked with high burdens of HCMV. We conclude that UL18 is a highly variable gene, where variation may alter the persistent burden of HCMV and/or the host response to that burden.
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Waters et al. (2022) conducted an observational in Human cytomegalovirus (HCMV) infection (n=60). HCMV UL18 variants was evaluated on Association of UL18 variants with HCMV antibody levels and T-cell responses. Specific HCMV UL18 variants, present in 95% of samples, were associated with altered HCMV antibody levels and T-cell responses in people with HIV and renal transplant recipients.
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