Shedding of Soluble Glycoprotein 1 Detected During Acute Lassa Virus Infection in Human Subjects
Abstract
Background Lassa hemorrhagic fever (LHF) is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. With a high rate of infection that may lead to morbidity and mortality, understanding how the virus interacts with the host's immune system is of great importance for generating vaccines and therapeutics. Previous work by our group identified a soluble isoform of the Lassa virus (LASV) GP1 (sGP1) in vitro resulting from the expression of the glycoprotein complex (GPC) gene. Though no work has directly been done to demonstrate the function of this soluble isoform in arenaviral infections, evidence points to immunomodulatory effects against the host's immune system mediated by a secreted glycoprotein component in filoviruses another class of hemorrhagic fever-causing viruses. A significant fraction of shed glycoprotein isoforms during viral infection and biogenesis may attenuate the host?s inflammatory response, thereby enhancing viral replication and tissue damage. Such shed glycoprotein mediated effects were previously reported for Ebola virus (EBOV) a filovirus that also causes hemorrhagic fever with nearly 90% fatality rates. The identification of an analogous phenomenon in vivo could establish a new correlate of LHF infection leading to the development of sensitive diagnostics targeting the earliest molecular events of the disease. Additionally, the reversal of potentially untoward immunomodulatory functions mediated by sGP1 could potentiate the development of novel therapeutic intervention.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 09, 2010
- Accession Number
- ADA532593
Entities
People
- Augustine Goba
- Daniel G. Bausch
- Jessica N. Grove
- Lina M. Moses
- Luis M. Branco
- Mambu Momoh
- Mohammed Fullah
- Randal J Schoepp
- Robert F. Garry
Organizations
- United States Army Medical Research Institute of Infectious Diseases