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Alphaviruses exist throughout the world and commonly cause natural encephalitis outbreaks among horses and humans. Generally, this disease is fatal in horses but only incapacitating in humans. Nevertheless, Venezuelan equine encephalitis virus (VEEV) was weaponized by the pre-1992 Soviet and pre-1969 United States biological warfare programs. Largely for this reason, alphaviruses are classified by the Centers for Disease Control and Prevention as Category B threat agents, or of second highest priority with respect to public health and national security. However, their potential as biothreat agents remains unclear as it would be technically difficult to weaponize and disperse them. Keywords: Togaviridae; alphavirus; category B agent; Eastern equine encephalomyelitis virus; EEEV; Venezuelan equine encephalitis virus; VEEV; Western equine encephalomyelitis virus; WEEV; encephalitis

Alphaviruses are classified by the Centers for Disease Control and Prevention as Category B agents, or of second highest priority with respect to public health and national security. The viruses exist throughout the world, and natural outbreaks among horses and humans are common. Generally, this disease is fatal in horses but only incapacitating in humans. Western equine encephalitis (WEE) virus has been researched and developed as a biological weapon by state-level programs in the past. Its potential as a terrorist threat agent remains unclear. Keywords: alphavirus; category B agent; Eastern equine encephalomyelitis; EEE; VEE; Venezuelan equine encephalitis; WEE; Western equine encephalomyelitis

Peritoneal macrophages from mice infected with herpes simplex virus type 2 (HSV-2) exhibited extrinsic antiviral resistance. When the macrophages were co-cultivated in vitro with virus-infected cells the yield of virus was reduced markedly. Activity was not present 1 to 2 days p.i., peaked at 3 to 4 days, declined by 7 days and was absent at 14 days after HSV-2 infection. The extrinsic antiviral activity was limited to the adherent peritoneal macrophage population. The macrophage antiviral activity was also dose-dependent, with approx. 10(6) macrophages (macrophage: host cell ratio of approx. 2:1) reducing virus plaques by greater than 90% and virus yield 1.5 to 3.0 log10. Comparable extrinsic antiviral activity was also exhibited by Corynebacterium parvum- or thioglycollate-elicited peritoneal macrophages. The macrophage activity was not species-specific, activity on Vero cells or syngeneic mouse embryo fibroblasts being comparable. Activity was also not virus-specific, as the active macrophages also inhibited vesicular stomatitis virus (VSV). The antiviral effects required viable macrophages; cell lysates did not inhibit virus growth.

Activated macrophages exhibit extrinsic antiviral activity (inhibition of virus replication in other cells) which may involve mechanisms similar to macrophage antitumor activity or macrophage-mediated immunosuppression. Peritoneal macrophages elicited in mice by Corynebacterium parvum vaccine suppressed the growth of herpes simplex virus (HSV) in infected cells by an interferon-independent mechanism. This was demonstrated by expression of activity against HSV-infected xenogeneic (Vero) cells. Culture supernatant fluids also did not mediate antiviral activity, and did not contain detectable levels of interferon (

Publisher Summary This chapter describes the assays for determining macrophage intrinsic antiviral activity and assessing extrinsic antiviral activity by measuring the ability of the macrophage to reduce virus growth in infected susceptible host cells in mixed culture. Virus titers are calculated from the plaque counts and dilutions. The virus titer sof macrophages lower than corresponding thermal inactivation controls suggest virus clearance from the macrophage or prolonged eclipse phase of virus in the macrophage. Slope of curve can be used to determine the rate of clearance. The number of plaques gives the number of infectious centers, that is, the number of macrophages containing infectious or potentially infectious virus. Extrinsic antiviral activity, the ability of certain mononuclear phagocytes to reduce virus growth in infected susceptible host cells on mixed culture, is another means by which macrophages may assist in host defense against viruses.