Rabies virus (RABV) infection leads to a fatal neurological outcome in humans and animals and is associated with major alterations in cellular gene expression. In this study, we describe the effects of RABV infection on the mRNA expression levels of two genes, encoding the Ca 2+ -binding proteins (Ca-BPs) calbindin D-28K ( Calb1 ) and calretinin ( Calb2 ), in the brains of BALB/c mice. Sixty 4-week-old mice were divided into two test groups and one control group. Mice were inoculated intramuscularly with either a street rabies virus (SRV) strain or a challenge virus standard (CVS-11) strain and sacrificed at 3-day intervals up to day 18 postinfection. A direct fluorescent antibody test (DFAT) was used to verify the presence of RABV antigen in brain tissues, and real-time quantitative PCR (RT-PCR) was used to assess gene expression. Infection with both RABV strains resulted in significant ( p < 0.05) increases in Calb1 and Calb2 expression in the test animals when compared with the controls at various time points in the study. Correlation analysis indicated very weak insignificant ( p > 0.05) negative and positive relationships, respectively, between Calb1 expression ( r = -0.04) and Calb2 expression ( r = 0.08) with viral load (CVS-11 strain). Insignificant ( p > 0.05) relationships were also observed Calb1 expression ( r = - 0.28) and Calb2 expression (r = 0.06) and viral load for the SRV strain. The observed alterations in Calb1 and Calb2 expression in this study indicate possible impairments in neuronal Ca 2+ buffering and Ca 2+ homeostasis as a result of RABV infection and, consequently, possible involvement of calbindin-D28K and calretinin in the neuropathogenesis of rabies.

Rabies virus (RABV) infection leads to a fatal neurological outcome in humans and animals and is associated with major alterations in cellular gene expression. In this study, we describe the effects of RABV infection on the mRNA expression levels of two genes encoding the Ca2+ binding proteins (Ca-BPs) Calbindin D-28K (Calb1) and Calretinin (Calb2) in the brains of BALB/c mice. Sixty, 4-week-old mice were divided into two test and one control group. Mice were inoculated intra-muscularly with either a street rabies virus (SRV) or Challenge virus standard (CVS-11) strain and sacrificed at 3-day intervals up to day 18 post infection. Direct fluorescent antibody test (DFAT) verified RABV antigen in the brain tissues and real time quantitative PCR (RT-PCR) was used to assess the gene expressions. Infection with both RABV strains resulted in relatively significant (p<0.05) increases in Calb1 and Calb2 expression in the test animals, when compared with the controls at various time points in the study. Correlation analysis indicated very weak insignificant (p>0.05) negative and positive relationships respectively between Calb1 expression (r = -0.04) and Calb2 expression (r = 0.08) with viral load (CVS-11 strain). Insignificant (p>0.05) relationships were also obtained between Calb1 expression (r= -0.28) and Calb2 expression (r = 0.06) with viral load for the SRV strain. The observed alterations in Calb1 and Calb2 expression in this study indicate possible impairments in neuronal Ca2+ buffering and Ca2+ homeostasis as a result of RABV infection and consequently, an implication of Calbindin-D28K and Calretinin in the neuro-pathogenesis of rabies.

Infection with the deadly rabies virus (RABV) leads to alteration of cellular gene expression. The RABV, similar to other neurodegenerative diseases may be implicated in neuronal death due to an imbalance in Ca 2+ homeostasis. Parvalbumin (PV) and Secretagogin (Scgn), two members of the Calcium-Binding Proteins (CBPs) are useful neuronal markers responsible for calcium regulation and buffering with possible protective roles against infections. This study investigated whether infection with rabies virus causes variance in expression levels of PV and Scgn using the Challenge virus standard (CVS) and Nigerian Street Rabies virus (SRV) strains. Forty-eight, 4-week-old BALB/c mice strains were divided into two test groups and challenged with Rabies virus (RABV) infection and one control group. The presence of RABV antigen was verified by direct fluorescent antibody test (DFAT) and real-time quantitative PCR (qRT-PCR) was used to assess PV and Scgn gene expression. Infection with both virus strains resulted in significant ( p < 0.05) increases in expression during early infection. Mid-infection phase caused reduced expression for both genes. However, as infection progressed to the terminal phase, a lower increase in expression was measured. Gene expression and viral load correlation indicated no positive relationship. Neurons with these CBPs may have a greater capacity to buffer calcium and be more resistant to degenerative changes caused by RABV. This implies that, when PV and Scgn expression levels are kept adequately high, the integrity of neurons may be maintained and degeneration caused by RABV infection may be prevented or stopped, hence, these are possible constituents of effective rabies therapy.