Drosophila have been used to model infection by the Sindbis virus, a mosquito-spread arthritogenic alphavirus that can also cause disease in humans. Sindbis virus is often studied as a prototypical alphavirus, a group which also includes chikungunya virus and several equine encephalitis viruses.
In Drosophila, blocking phagocytosis, or ablating hemocytes before infection with Sindbis virus does not affect survival or viral load, which is unusual as phagocytosis is a core mechanism of the fly innate immune system. Similarly, blocking autophagy by knocking down Atg7 also has little effect.
A screen for RNA processing factors that inhibit RNA viruses found that knocking down two cofactors of RNA exosomal degradation complexes, Mtr4 and Zcchc7, significantly increase the rate of infection by Sindbis virus, vesicular stomatitis virus, and Rift Valley fever virus. Mtr4 has a high-scoring ortholog in humans, Mtr4, and Zcchc7 has a low-scoring ortholog, Zcchc7.
[updated June 2019 by FlyBase; FBrf0222196]
Alphaviruses cause primarily two types of disease: encephalitis and polyarthritis. The virulence of SINV is due to the induction of apoptosis in neurons. Two genes that influence apoptosis, Bcl-2 and Bax, have been studied in relation to neurovirulence. An avirulent strain of SINV did not induce apoptosis in cultured cells expressing Bcl-2, whereas a neurovirulent strain did. (Atkins and Sheahan 2016 and references therein, pubmed:27028153.) The defining feature of most alphaviral arthritides is chronic, episodic, often debilitating joint pain (polyarthralgia and/or polyarthritis), which is often associated with fatigue. Although most patients progressively recover within several weeks, in some the disease can last for months. Chronic alphaviral rheumatic disease probably arises from inflammatory responses stimulated by the virus persisting in joint tissues, despite robust antiviral immune responses. (Suhrbier et al. 2012, pubmed:22565316.)
Phylogenetic analyses and older serological cross-reactivity studies suggest two major clusters for alphaviruses ('Old World' and 'New World' alphaviruses according to the geographical placement of the majority of the viruses within the groups), and four subgroups (Semliki Forest virus, Venezuelan Equine Encephalitis virus, Eastern Equine Encephalitis virus and Western Equine Encephalitis virus complex). SINV belongs to the Western Equine Encephalitis virus complex and is the only representative of this group outside of Americas. Notably, WEEV has been evolved as a product of an ancient recombination event between SINV-like (envelope) proteins and EEEV-like (non-structural proteins) viruses. (Adouchief et al. 2016 and reference therein, pubmed:26990827.)
SINV is a spherical (T=4) virus of 70 nm in diameter. It enters target cells in a receptor mediated manner in clathrin coated vesicles. Translation and assembly of nucleocapsid occur free in the cytosol, while replication of RNA requires specific membranous replication complexes. Virion assembly is completed at the plasma membrane where a lipid membrane and the glycoprotein complexes are acquired. (Adouchief et al. 2016 and reference therein, pubmed:26990827.)
