Clearance of virus infection from the CNS

Abstract

Viruses that cause encephalomyelitis infect neurons and recovery from infection requires noncytolytic clearance of virus from the nervous system to avoid damaging these irreplaceable cells. Several murine model systems of virus infection have been used to identify clearance mechanisms. Quantitative analysis of Sindbis virus clearance over 6 months shows three phases: day 5-7, clearance of infectious virus, but continued presence of viral RNA; day 8-60, decreasing levels of viral RNA; day 60-180, maintenance of viral RNA at low levels. Antiviral antibody and interferon-γ have major roles in clearance with a likely role for IgM as well as IgG antibody. Long-term residence of virus-specific immune cells in the nervous system is necessary to prevent virus reactivation.

Figure 1

Schematic quantitative diagram of the phases of alphavirus clearance from the brain and spinal cord of mice. The period of detection of infectious virus by plaque assay is shaded red. The appearance, clearance and persistence of viral RNA as detected by quantitative RT-PCR is indicated by the dashed black line (Metcalf and Griffin, unpublished).

Figure 2

Quantitation of CD4⁺ T cells, CD8⁺ T cells and CD19⁺ B cells present at different times in the brain in response to alphavirus infection (Metcalf et al., unpublished).

Figure 3

Effect of various immunodeficiencies on clearance of infectious virus from the brain after alphavirus infection of mice. SCID, severe combined immunodeficiency; BKO, IFN-β-deficient; μMT, antibody-deficient; GKO, interferon-γ-deficient; WT B6, wild type C57BL/6 [13].