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 alphavirus endemic in parts of Central and South America. The disease is transmitted by mosquitoes, and the natural reservoir is the small rodent population, with epidemics occurring in horses and occasionally humans. Following infection, VEEV replicates in lymphoid tissues prior to invasion of the central nervous system. Treatment of VEEV-infected BALB/c mice with polyethylene glycol-conjugated alpha interferon (PEG IFN-alpha) results in a greatly enhanced survival from either a subcutaneous or an aerosol infection. Virus is undetectable within PEG IFN-alpha-treated individuals by day 30 postinfection (p.i.). Treatment results in a number of changes to the immune response characteristics normally associated with VEEV infection. Increased macrophage 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. normally associated with VEEV infection is absent in PEG IFN-alpha-treated mice. The high tumor necrosis factor alpha production by macrophages from untreated mice is greatly diminished in PEG IFN-alpha-treated mice. These results suggest key immunological mechanisms targeted by this lethal alphavirus that can be modulated by prolonged exposure to IFN-alpha.
Lukaszewski
R A
RA
CBD, Porton Down, Salisbury, Wiltshire SP4 0JQ, United Kingdom. rlukaszewski@hotmail.com
Brooks
T J
TJ
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D000998:Antiviral Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002460:Cell Line; D006224:Cricetinae; D004666:Encephalitis Virus, Venezuelan Equine / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity; D004685:Encephalomyelitis, Venezuelan Equine / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D019570:Inhalation Exposure; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000627:therapeutic use; D015847:Interleukin-4 / Q000627:therapeutic use; D037181:Lectins, C-Type; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D014774:Virulence; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D018664:Interleukin-12; D015847:Interleukin-4; D037181:Lectins, C-Type; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D000099192:CD69 Antigens