[Frontiers in Bioscience E5, 154-166, January 1, 2013]

How hantaviruses modulate cellular pathways for efficient replication?

Islam T. M. Hussein1, Mohammad A Mir1

1Department of Microbiology, Molecular Genetics and Immunology, University of Kansa Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66103, USA

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Modulation of the innate immune response
3.1. Cytoplasmic tail of Gn protein
3.2. Non-structural protein
3.3. Nucleocapsid protein
4. Modulation of the host mRNA degradation pathway for cap snatching and transcription initiation
5. Modulation of the host cell translation machinery
6. Modulation of the cytopskeletal proteins for proper trafficking and assembly
7. Modulation of the apoptosis signaling pathways
8. Modulation of the SUMOylation machinery for proper N subcellular localization and assembly
9. Conclusion and future perspectives: 10. References

1. ABSTRACT

Hantaviruses are zoonotic category-A pathogens that cause highly fatal diseases in humans. The hantaviral genome encodes three viral proteins: RNA-dependent RNA polymerase (RdRp or L protein), nucleocapsid protein (N), and a glycoprotein precursor (GPC), which is post-translationally cleaved into two surface glycoproteins Gn and Gc. The cytoplasmic tail of Gn interferes with interferon signaling pathways. N is a multifunctional molecule that was shown to be involved in the transcription and translation of viral proteins. N binds to the host mRNA caps and protects the degradation of mRNA 5' termini, which are later snatched and used as primers by the viral RdRp during transcription initiation. N also seems to lure the host translation machinery for the preferential translation of viral transcripts. Moreover, N was shown to delay the induction of cellular apoptosis and facilitate the transport and localization of viral ribonucleoproteins (RNPs) by exploiting the cellular cytoskeleton and SUMOlyation machinery. Therefore, with their limited protein coding capacity, hantaviruses have evolved several strategies to modulate cellular pathways for their efficient replication.