Pegylated alpha interferon is an effective treatment for virulent Venezuelan equine encephalitis virus and has profound effects on the host immune response to infection

Venezuelan equine encephalitis virus (VEEV) is a highly infectious alphavir us endemic in parts of Central and South America. The disease is transmitte d by mosquitoes, and the natural reservoir is the small rodent population, with epidemics occurring in horses and occasionally humans. Following infec tion, VEEV replicates in lymphoid tissues prior to invasion of the central nervous system. Treatment of VEEV-infected BALB/c mice with polyethylene gl ycol-conjugated alpha interferon (PEG IFN-alpha) results in a greatly enhan ced survival from either a subcutaneous or an aerosol infection. Virus is u ndetectable within PEG IFN-alpha-treated individuals by day 30 postinfectio n (p.i.). Treatment results in a number of changes to the immune response c haracteristics normally associated with VEEV infection. Increased macrophag e activation occurs in PEG IFN-alpha-treated BALB/c mice infected with VEEV , The rapid activation of splenic CD4, CD8, and B cells by day 2 p.i. norma lly associated with VEEV infection is absent in PEG IFN-alpha-treated mice. The high tumor necrosis factor alpha production by macrophages from untrea ted mice is greatly diminished in PEG IFN-or-treated mice. These results su ggest key immunological mechanisms targeted by this lethal alphavirus that can be modulated by prolonged exposure to IFN-alpha.