Genomic analysis finds a surprising association between ciHHV-6 and two genes

A genomic analysis of samples from 141,431 Chinese women found a highly significant association between ciHHV-6 and a variant in the MLCI-MOV10L region.  The MLC1 gene is involved in myeloid cell differentiation and the MOV10L1 gene may allow for more efficient integration during spermatogenesis.

Samples from pregnant Chinese women undergoing prenatal genetic testing was used to analyze genetic associations and viral infections. Hepatitis B was the most common infection, followed by endogenous retrovirus K113. HHV-6 was next, with a prevalence of 0.8%.

An intronic variant, rs73185306  in the MLC1-MOV10L1 region was highly associated with ciHHV6A/B group but not the “low abundance” HHV-6A/B positive cases.

It is not clear what percentage of the “low abundance” HHV-6 are from reactivated HHV-6 or possibly, from mothers carrying ciHHV6 fetuses.

In the Hall 2008 study, they determined that of the congenital infections in cord blood, 86% resulted from ciHHV6 and 14% were from active infections, passed to the fetus transplacentally by a mother with ciHHV6 (Hall 2008).

The MLC1 gene is upregulated during herpesvirus infections of CMV, EBV and HHV-8 and the MOV10L1 gene is associated with platelet distribution and is a PIWI interacting RNA helicase that is active during spermatogenesis, functioning as a repressor of retrotransposons. The authors suspect that the PIWI-interacting RNA represses HHV-6 integration, and that polymorphisms of this gene allows for more efficient integration of HHV-6 during spermatogenesis.

The authors noted no others genome-wide SNP associations with other viruses.

Read the full paper: Liu 2018