Recent advances in hantavirus molecular biology and disease

Abstract

Hantaviruses are emerging zoonotic pathogens that belong to the Bunyaviridae family. They have been classified as category A pathogens by CDC (centers for disease control and prevention). Hantaviruses pose a serious threat to human health because their infection causes two highly fatal diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). These pathogens are transmitted to humans through aerosolized excreta of their infected rodent hosts. Hantaviruses have a tripartite-segmented negative-sense RNA genome. The three genomic RNA segments, S, M, and L, encode a nucleocapsid protein (N), a precursor glycoprotein that is processed into two envelope glycoproteins (Gn and Gc) and the viral RNA-dependent RNA polymerase (RdRp), respectively. N protein is the major structural component of the virus, its main function is to protect and encapsidate the three genomic RNAs forming three viral ribonucleocapsids. Recent studies have proposed that N in conjunction with RdRp plays important roles in the transcription and replication of viral genome. In addition, N preferentially facilitates the translation of viral mRNA in cells. Glycoproteins, Gn and Gc, play major roles in viral attachment and entry to the host cells, virulence, and assembly and packaging of new virions in infected cells. RdRp functions as RNA replicase and transcriptase to replicate and transcribe the viral RNA and is also thought to have endonuclease activity. Currently, no antiviral therapy or vaccine is available for the treatment of hantavirus-associated diseases. Understanding the molecular details of hantavirus life cycle will help in the identification of targets for antiviral therapeutics and in the design of potential antiviral drug for the treatment of HFRS and HCPS. Due to the alarming fatality of hantavirus diseases, development of an effective vaccine against hantaviruses is a necessity.