Intracranial Inoculation Is More Potent Than Intranasal Inoculation for Inducing Optic Neuritis in the Mouse Hepatitis Virus-Induced Model of Multiple Sclerosis

Singh, Manmeet; Khan, Reas S.; Dine, Kimberly; Das Sarma, Jayasri; Shindler, Kenneth S.

While intrancranial inoculation was shown previously to induce optic neuritis (Shindler et al., 2008 (Shindler et al., , 2011 , effects of intranasal inoculation with RSA59 on optic nerve pathology were not reported. In the current study, intranasal infection by RSA59 at the same dose used for intracranial inoculation was not able to induce any neuropathogenesis, either in optic nerve or spinal cord. Earlier studies with several other strains showed that intranasal inoculation of MHV can cause CNS disease, but much higher concentrations of virus were used than in intracranial inoculation studies. MHV-JHM enters the central nervous system (CNS) via the olfactory after intranasal inoculation . The intranasal inoculation of JHM strain can lead to encephalitis and demyelination. The OBLV strain of MHV can infect the main olfactory bulb (Schwob et al., 2001) . Intranasal inoculation of MHV-A59 can lead to hepatitis with measurable viral load in brain as well (Hemmila et al., 2004) . These studies did not report optic nerve pathogenesis following intranasal inoculation although it is not known if that was examined. There are several possible reasons that we did not see retinal infection or optic nerve inflammation and demyelination lesions after intranasal inoculation. Most likely, the dose of virus may have been too low to cause the pathogenesis. This finding was not unexpected in the spinal cord, where previous studies showed higher doses were necessary. However, based on the high levels of protein accumulation in optic nerve and eye following intranasal inoculation (Khan et al., 2017) , it was anticipated that RSA59 would also preferentially accumulate in the eye, but results suggest that higher doses are likely required. Alternatively, the intranasal inoculation may be less effective for inducing optic neuritis and retinal lesions than the intracerebral route because of the longer distance required for the virus to travel to the eye if it travels via axonal transport and neuronneuron spread similar to what has been observed following intracranial inoculation (Das Sarma et al., 2009; Shindler et al., 2011) .