Abstract
Alphavirus nsP2 proteins are multifunctional and essential for viral replication. The protease role of nsP2 is critical for virus replication as only the virus protease activity is used for processing of the viral non-structural polypeptide. Chikungunya virus is an emerging disease problem that is becoming a world-wide health issue. We have generated purified recombinant chikungunya virus nsP2 proteins, both full length and a truncated protease domain from the C-terminus of the nsP2 protein. Enzyme characterization shows that the protease domain alone has different properties compared with the full length nsP2 protease. We also show chikungunya nsP2 protease possesses different substrate specificity to the canonical alphavirus nsP2 polyprotein cleavage specificity. Moreover, the chikungunya nsP2 also appears to differ from other alphavirus nsP2 in its distinctive ability to recognize small peptide substrates.
Highlights
Chikungunya virus (CHIKV), the causative agent of chikungunya fever, is an Alphavirus belonging to the family Togaviridae, that was originally isolated in Tanzania, Africa [1]
Results consistently showed that the non-structural protein 2 (nsP2) proteins were expressed as inclusion bodies under ‘high’ temperature culturing conditions (37 ◦C), and only partially expressed in a soluble form at 22 ◦C
The protease role of nsP2 is critical for virus replication as only the virus protease activity is used for processing the viral non-structural polypeptide
Summary
Chikungunya virus (CHIKV), the causative agent of chikungunya fever, is an Alphavirus belonging to the family Togaviridae, that was originally isolated in Tanzania, Africa [1]. In Asia and elsewhere transmission is generally maintained in an urban human–mosquito–human cycle [4] with Aedes genus mosquitoes being the major vectors, especially Ae. aegypti and Ae. albopictus. Ae. albopictus is one of the world’s 100 most invasive species, increasing the risk of CHIKV emerging or re-emerging and becoming a major health problem around the world [4]. This has been exemplified by the recent introduction of CHIKV into the Americas, where, within a short time, more than a million suspected cases of chikungunya fever are believed to have occurred [7]. Chikungunya fever is typically characterized by headache, high fever, skin rash and nausea as well as joint pain that can be severe and long lasting, and, rare, fatalities have been reported [8]
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