Induction of Rabies Virus Infection in Mice Brain may Up and Down Regulate Type II Interferon gamma via epigenetic modifications

Abdulazeez, Maryam; Kia, Grace S. N.; Abarshi, Musa M.; Muhammad, Aliyu; Ojedapo, Comfort E.; Atawodi, Joy Cecilia; Dantong, David; Kwaga, Jacob K. P.

As feared and deadly human diseases globally, Rabies virus contrived mechanisms to escape early immune recognition via suppression of the interferon response. This study, preliminarily investigated whether Rabies virus employs epigenetic mechanism for the suppression of the interferon using the Challenge virus standard (CVS) strain and Nigerian street Rabies virus (SRV) strain. Mice were challenged with Rabies virus (RABV) infection, and presence of RABV antigen was assessed by direct fluorescent antibody test (DFAT). A real time quantitative Polymerase chain reaction (qRT-PCR) was used to measure the expression of type II interferon gamma (IFNG) and methylation specific quantitative PCR for methylation analysis of 1FNG promoter region. Accordingly, DNA methyltransferase (DNMT) and histone acetyltransferase (HAT) enzymes activities were determined. RABV antigen was detected in all infected samples. A statistically significant increase (p < 0.05) in mRNA level of IFNG was observed at the onset of the disease and a decrease as the disease progressed. An increase in methylation in the test groups from the control group was observed, with a fluctuation in methylation as the disease progressed. DNMT and HAT activities also agree with methylation as there was an observed increase activity in test group compared with control group. Similar fluctuation pattern was observed in both CVS and SRV groups as the disease progressed with HAT, being the most active proportionally. This study suggests that epigenetic modification via DNA methylation and histone acetylation may have played a role in the expression of type II interferon gamma in Rabies virus infection. [Figure: see text]