Studies of the pathogenesis of Dugbe virus in normal and in immunosuppressed mice
Susceptibility to lethal infection with the KT281/75 strain of the tick-borne nairovirus, Dugbe (DUG) virus, was similar in an outbred strain and several inbred strains of mice. For the outbred strain, both neural and extraneural routes of inoculation of virus resulted in lethal infection, but susceptibility decreased with age and only intracranial inoculation produced a lethal infection in adults. In newborn mice, subcutaneous (s.c.) inoculation of virus (analogous to a tick-bite) produced a slowly developing disseminated infection with virus not reaching maximum titres in the brain until 8 days after inoculation. In contrast, in intranasally (i.n.) inoculated animals virus spread rapidly from the upper respiratory tract to the brain by 2 days after inoculation, in the absence of a detectable viremia. No viremia was detected in s.c. or i.n. inoculated adults: in the former, virus replicated only at the site of inoculation; in the latter, virus replicated in the respiratory tract, later spreading to the brain. Immunosuppression of i.n. inoculated adult mice with cyclophosphamide produced some mortality, indicating that host defenses are important in protecting the adult. Differences in virulence were exhibited between two tick isolates of Dugbe virus (strains ArD16095 and ArD44313), a human isolate (IbH11480) and the laboratory strain KT281/75. Virulence differences varied with the route of inoculation. The human isolate, unlike the other isolates, was lethal for adult mice by the intranasal route without immunosuppression. The similarity between the pattern of DUG virus infection in the mouse with that of other, more pathogenic, nairoviruses suggests that, although hemorrhagic disease was not observed, ours may be a useful model for studying the genetic basis of nairovirus virulence and for testing vaccines and anti-viral drugs.
KeywordsNewborn Mouse Human Isolate Intranasal Route Lethal Infection Detectable Viremia
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