Tracking and elucidating alphavirus host protein interactions

27 Jul

The alphavirus single-stranded, positive-sense RNA (( )RNA) genome of approximately 11.8 kb is flanked by a 5’- and a 3’-untranslated region (UTR) and contains two open reading frames (ORFs).

The 5’ ORF is directly translated from the genomic RNA into a polyprotein that contains the four nonstructural proteins (ns P) 1234, which is proteolytically cleaved into individual ns Ps (Figure 1).

As a consequence, alphavirus–host interactions are now understood in much more molecular detail, and important novel mechanisms have been elucidated.

It has become clear that alphaviruses not only cause a general host shut-off in infected vertebrate cells, but also specifically suppress different host antiviral pathways using their viral nonstructural proteins, ns P2 and ns P3.

Since the discovery of CHIKV in 1952, sporadic CHIKV outbreaks have been recorded in central Africa and southern Asia [12].

However, from 2001 onwards several major outbreaks have occurred affecting the islands of Mauritius, Madagascar, Mayotte, and Reunion.

Ns P4 is the RNA-dependent RNA polymerase [24,25], which is the first ns P to be proteolytically cleaved from the polyprotein.

Alphaviruses can have a very diverse vertebrate and invertebrate host range [7].In 20, CHIKV was again transmitted on European territory in the southeast of France [15,16].In October 2013, the first cases of autochthonous CHIKV transmission in the western hemisphere were detected in the French Caribbean [17].Ns P2 is the protease that cleaves the nonstructural polyprotein, has helicase activity and a methyltransferase-like domain [22].The function of ns P3 in viral RNA replication is not understood, yet the protein is an essential component of the RC and is highly phosphorylated [23].