Treatment of Sindbis Virus-Infected Neurons with Antibody to E2 Alters Synthesis of Complete and nsP1-Expressing Defective Viral RNAs
Year: 2022
Type: article
Abstract: Alphaviruses are important causes of viral encephalomyelitis without approved treatments or vaccines. Antibody to the Sindbis virus (SINV) E2 glycoprotein is required for immune-mediated noncytolytic virus clearance from neurons. We used direct RNA nanopore sequencing to evaluate how anti-E2 antibody affects SINV replication at the RNA level. Antibody altered the viral RNAs produced by decreasing the proportion of subgenomic relative to genomic RNA and suppressing production of a previously unrecognized defective viral genome (DVG) encoding nsP1, the viral RNA capping enzyme. Antibody-treated neurons released a lower proportion of SINV particles with capped genomes necessary for translation and infection. Decreased nsP1 DVG production in antibody-treated neurons led to lower expression of nsP1 protein, decreased genome capping efficiency, and release of fewer infectious virus particles. Capping was increased with exogenous expression of the nsP1 DVG. These studies identify a novel alphavirus DVG function and new mechanism for antibody-mediated control of virus replication.
Source: mBio
Authors: Jane X. Yeh, Yunfan Fan, Maggie L. Bartlett, Xiaoyan Zhang, Norah Sadowski, Debra A. Hauer, Winston Timp, Diane E. Griffin
Institution: Johns Hopkins University
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,900
Awards: Role of CD4 T cells in fatal alphavisus encephalomyelitis, Cellular Signaling Pathways Involved in Antibody-Mediated Clearance of Sindbis Virus from Neurons, Direct nanopore detection of modified RNA to probe structure and dynamics, Control of alphavirous replacation in the nervous system, Malaria and Mosquito/Tick-borne Diseases, The Molecular and Cellular Basis of Infectious Diseases (MCBID) Program
OpenAlex ID: W4294916284