Abstract
Nairobi sheep disease virus (NSDV; also called Ganjam virus in India) is a bunyavirus of the genus Nairovirus. It causes a haemorrhagic gastroenteritis in sheep and goats with mortality up to 90%. The virus is closely related to the human pathogen Crimean-Congo haemorrhagic fever virus (CCHFV). Little is currently known about the biology of NSDV. We have generated specific antibodies against the virus nucleocapsid protein (N) and polymerase (L) and used these to characterise NSDV in infected cells and to study its distribution during infection in a natural host. Due to its large size and the presence of a papain-like protease (the OTU-like domain) it has been suggested that the L protein of nairoviruses undergoes an autoproteolytic cleavage into polymerase and one or more accessory proteins. Specific antibodies which recognise either the N-terminus or the C-terminus of the NSDV L protein showed no evidence of L protein cleavage in NSDV-infected cells. Using the specific anti-N and anti-L antibodies, it was found that these viral proteins do not fully colocalise in infected cells; the N protein accumulated near the Golgi at early stages of infection while the L protein was distributed throughout the cytoplasm, further supporting the multifunctional nature of the L protein. These antibodies also allowed us to gain information about the organs and cell types targeted by the virus in vivo. We could detect NSDV in cryosections prepared from various tissues collected post-mortem from experimentally inoculated animals; the virus was found in the mucosal lining of the small and large intestine, in the lungs, and in mesenteric lymph nodes (MLN), where NSDV appeared to target monocytes and/or macrophages.
Highlights
The genus Nairovirus, of the family Bunyaviridae, includes viruses known to be pathogenic in humans or livestock, as well as viruses whose mammalian and arthropod hosts are still to be determined
These data show that all the detectable L protein in infected cells is present as the full-length protein, and argue strongly against autoproteolytic cleavage which would result in the N- and C-terminus being in different proteins
The same results were obtained in Vero and BHK-21 clone 13 cells infected with either the pathogenic (NSDVi) or the cell-culture adapted (NSDVu) isolate, which strengthens the biological relevance of this finding
Summary
The genus Nairovirus, of the family Bunyaviridae, includes viruses known to be pathogenic in humans or livestock, as well as viruses whose mammalian and arthropod hosts are still to be determined. An Asian virus causing the same disease is called Ganjam virus (GV) (reviewed in [13]); based on genetic and serological studies, it has been identified as a variant of NSDV [12, 14]. Sheep and goats are the only known mammalian reservoir of NSDV [8, 9]; other livestock are refractory to disease even when deliberately infected [6]. In most cases, infected animals which recover from disease remain refractory to subsequent infections for several years or even the lifetime of the animal [6]
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