The role of host immunocompetence in neuroinvasion of Sindbis virus

Viral infections of the central nervous system (CNS) following peripheral i noculation of Sindbis viruses were studied. The use of viral strains, which vary in their neuroinvasive and neurovirulent properties, and various stra ins of mice, which differ in immunocompetence, revealed several pathways of viral neuroinvasion in adult mice. A genetic-trait dependent mechanism was exhibited by the neuroinvasive viruses, showing a similar pattern in all m ice strains tested. A second mechanism, dependent on a prolonged high viral load, was exhibited by a noninvasive variant in Severe Combined ImmunoDefi cient (SCID) mice. The absence of antiviral antibodies in SCID mice allowed the maintenance of a longterm high viremia, leading to a random entry to t he CNS and proliferation in brain tissue. An additional pathway for neuroin vasion was induced upon disruption of the blood-brain barrier activity by e xogenous reagents and was demonstrated in cases of short lived high viremia of noninvasive viruses.