Materials and Methods 2.1. Repeated intraperitoneal passive transfer of immune serum resulted in maintenance of brain computer virus RNA, with no detectable infectious computer virus, for several weeks. When passive antibody transfer was halted, antibody levels declined and infectious computer virus was again detectable in the brain. In aged immunocompetent mice, previously infected with SFV, immunosuppression of antibody responses many months after initial contamination also resulted in renewed ability to detect infectious computer virus in the brain. In summary, antiviral antibodies control and determine whether infectious computer virus is usually detectable in the brain but immune responses cannot obvious this contamination from the brain. Functional computer virus RNA capable of generating infectious computer virus persists and if antibody levels decline, infectious computer virus is usually again detectable. Keywords: Semliki Forest computer virus, alphavirus, persistence 1. Introduction Most central nervous system (CNS) infections initiated by RNA viruses are clinically acute. Based on infectivity assays in experimental model systems, levels of infectious computer virus are rapidly reduced to below detectable levels by immune responses. CNS immune responses are highly specialized and regulated [1,2]; the resting CNS, is usually separated from your blood by the tight endothelial cell junctions of the blood-brain barrier (BBB), it lacks organized lymphoid tissue, has limited antigen presentation capacity [3], limited major histocompatibility complex (MHC) expression [4,5], no antibodies, no functional complement system and an immunosuppressive cytokine environment [6,7]. Computer virus contamination of the CNS can nevertheless give rise to florid immune responses. The CNS is also highly specialised in that it contains many long-lived cells with reduced propensity to undergo apoptosis upon computer virus contamination predisposing, as we have long argued, to computer virus persistence [8]. Semliki Forest computer virus (SFV) provides a well-characterised and tractable model of computer virus encephalitis [9,10]. SFV is efficiently neuroinvasive, allowing study of CNS events without direct intracerebral inoculation and disturbance of the BBB. SFV strains vary in their virulence MI 2 and can produce acute fatal panencephalitis or non-fatal subacute encephalitis with MI 2 lesions of inflammatory demyelination. SFV inoculated intraperitoneally first replicates in several tissues resulting in a high titre plasma viraemia from which computer virus crosses the BBB to establish small perivascular foci of CNS contamination and infectious computer virus is usually detectable in the brain from day two to ten [11]. SFV predominantly infects neurons and oligodendrocytes, but replication is restricted in the mature neurons of the adult mouse brain [11,12,13]. Immune system clearance of detectable infectious computer virus is followed by the appearance of lesions MI 2 of inflammatory demyelination which are dependent upon the presence of CD8+ T cells [14]. Following recovery from your acute contamination, while infectious computer virus is usually no-longer detectable, computer virus RNA is usually detectable in the brain for many months [15] and there is continued intrathecal antibody synthesis by plasma cells [16,17]. Similarly, after Sindbis computer virus (SINV) contamination of mice, computer virus RNA in the brain and intrathecal B-cells and IgG secretion are observed many months after the acute infection MMP11 has resolved [18,19]. In athymic mice, which lack T lymphocytes and which produce only anti-viral IgM, titers of infectious SFV in the blood are rapidly reduced to undetectable levels whereas in the brain, high titres of infectious computer virus remain for months [20]. In SCID mice, with no antibody and no functional T or B cells, high titres of infectious SFV are detectable in both the blood and the brain for several weeks [21]. However, passive transfer of polyclonal anti-SFV antibody rapidly reduces the high levels of infectious computer virus in the blood and the brain to MI 2 below the level of detection of the assay. Similarly, a single dose of polyclonal or monoclonal antibody also renders infectious SINV undetectable in the CNS of SCID mice [22]. What remains unclear is whether MI 2 the alphavirus RNA which persists in the brain can generate infectious computer virus. Here we show, using passive transfer of antibodies to SFV infected SCID mice and through immunosuppression of aged mice which have recovered from SFV contamination, that this viral RNA which persists in the mouse brain is usually capable or regenerating infectious computer virus. 2. Materials and Methods 2.1. Computer virus The avirulent A7(74) strain of Semliki Forest computer virus was used in this study [11]. All mice were inoculated.