Comparative Characterization of the Sindbis Virus Proteome from Mammalian and Invertebrate Hosts Identifies nsP2 as a Component of the Virion and Sorting Nexin 5 as a Significant Host Factor for Alphavirus Replication
Abstract
Recent advances in mass spectrometry methods and instrumentation now allow for more accurate identification of proteins in low abundance. This technology was applied to Sindbis virus, the prototypical alphavirus, to investigate the viral proteome. To determine if host proteins are specifically packaged into alphavirus virions, Sindbis virus (SINV) was grown in multiple host cells representing vertebrate and mosquito hosts, and total protein content of purified virions was determined. This analysis identified host factors not previously associated with alphavirus entry, replication, or egress. One host protein, sorting nexin 5 (SNX5), was shown to be critical for the replication of three different alphaviruses, Sindbis, Mayaro, and Chikungunya viruses. The most significant finding was that in addition to the host proteins, SINV nonstructural protein 2 (nsP2) was detected within virions grown in all host cells examined. The protein and RNA-interacting capabilities of nsP2 coupled with its presence in the virion support a role for nsP2 during packaging and/or entry of progeny virus. This function has not been identified for this protein. Taken together, this strategy identified at least one host factor integrally involved in alphavirus replication. Identification of other host proteins provides insight into alphavirus-host interactions during viral replication in both vertebrate and invertebrate hosts. This method of virus proteome analysis may also be useful for the identification of protein candidates for host-based therapeutics.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 15, 2018
- Source ID
- 10.1128/jvi.00694-18
Entities
People
- Amanda Piper
- Andy Kilianski
- Farooq Nasar
- Gabrielle Boyd
- José M. C. Ribeiro
- Raquel Hernandez
- Ricardo Vancini
- Ryan Schuchman
- Thomas R. Sprague
- Trevor Glaros
Organizations
- Edgewood Chemical Biological Center
- National Institute of Allergy and Infectious Diseases
- North Carolina State University
- United States Army Medical Research Institute of Infectious Diseases