Phatogenesis and the role of innate immunity in emerging patogen (Crimean Congo Heamorraghic fever virus)

Ali Mirazimi, Lundkvist, Åke; Andersson, Ida , Simon, Melinda

KCB/ Swedish Institute for Infectious Disease Control, Sweden

Crimean Congo hemorrhagic fever virus (CCHFV) belongs to the genus Nairovirus within the family Bunyaviridae and is the causative agent of severe hemorrhagic fever. The factors determining the virulence and pathogencity among the members of the Bunyaviridae family are poorly understood. Both innate and acquired immunity are suggested to be involved in controlling the infection. Innate immunity, which is rapidly activated by many viral infections, is expected to play a predominant role in controlling the initial events of the infections. Previous studies have demonstrated that the human interferons have an antiviral effect against a number of RNA viruses, including some members of the Bunyaviridae family. However, little is known about the molecular mechanisms of this antiviral action. The interferon (IFN)-induced MxA protein has been shown to have an inhibitory effect on several members of the Bunyaviridae family, but the effect of MxA against the members of nairovirus has not previously been studied. Here, we report that human MxA has antiviral activity against CCHFV. Our results demonstrate that MxA, by interacting with CCHFV nucleocapsid protein, prevents replication of CCHFV viral RNA and thereby inhibits the production of new infectious virus particles.

Another important component/molecule in innate immunity system is Nitric Oxide (NO). The mechanism of many events induced by NO is well studied. An antimicrobiological activity of NO is suggested for bacteria and protozoa, but less is known about the effect of NO in viral infections. NO has been shown to have an antiviral effect against mainly DNA viruses, but also against certain RNA viruses such as the Japanese encephalitis. Here, we report that NO can inhibit the replication cycle of CCHF virus in Vero cells.

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