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

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. Graphical abstract.

Rabies virus infection in mice up-regulates B7-H1 via epigenetic modifications.

Rabies virus infection is an endemic disease which remains central to public health issues. The presence of epigenetics associated with the over-expression of B7-H1 in mice brain infected with rabies virus was investigated for the first time. A significant increase (p < 0.05) in mRNA level of B7-H1 as the disease progressed was observed. The percentage of methylated region was significantly (p < 0.05) higher in infected tissues relative to uninfected. DNA methyltransferase (DNMT) and histone acetylase (HAT) activities were also significantly (p < 0.05) higher in most infected brain tissues. HAT had a relatively higher proportion than DNMT when compared to the normal. Paradoxically, it can be inferred that the rabies virus uses epigenetic mechanisms as a means of manipulating host genes, as there was an increase in global DNMT and HAT activities with concomitant increase in B7-H1 promoter methylation and expression.