Hantaviral Proteins: Structure, Functions, and Role in Hantavirus Infection

Abstract

Hantaviruses are the members of the family Bunyaviridae that are naturally maintained in the populations of small mammals, mostly rodents. Most of these viruses can easily infect humans through contact with aerosols or dust generated by contaminated animal waste products. Depending on the particular Hantavirus involved, human infection could result in either hemorrhagic fever with renal syndrome or in Hantavirus cardiopulmonary syndrome. In the past few years, clinical cases of the Hantavirus caused diseases have been on the rise. Understanding structure of the Hantavirus genome and the functions of the key viral proteins are critical for the therapeutic agents' research. This paper gives a brief overview of the current knowledge on the structure and properties of the Hantavirus nucleoprotein and the glycoproteins.

Keywords: Hantavirus; MxA protein; glycoprotein; nucleocapsid protein; reassortment.

FIGURE 1

Hantavirus transcription, replication and translation. (A) Hantavirus transcription. Transcription occurs through a prime and realign mechanism. Cellular mRNA is cleaved by either Hantavirus RNA-dependent RNA polymerase (RdRp) or cellular endonucleases in a process called cap snatching, thus forming a capped primer (m⁷GpppN_n). It is this capped primer that initiates transcription by aligning its guanidine to the 3′ cytosine of the vRNA. After synthesis of several nucleotides, the nascent RNA slips back and realigns. Final elongation then takes place, producing an extra copy of viral mRNA. (B) Replication of Hantavirus RNA. Replication takes place in cytoplasm of the infected cell, using prime and realign mechanism. RdRp attached to the 3′ end of vRNA aligns guanidine triphosphate (pppG) residue to the first cytosine of the virus RNA and synthesizes the first three nucleotides of the new cRNA strand. The nascent RNA slips back and realigns after successive addition of bases. Then, final elongation takes place, resulting in production of the full length cRNA. In turn, this positive strand anti-genomic cRNA serves as a template for producing a large amount of the new strands of vRNA. (C) Hantavirus transcription and translation. Negative sense viral RNA serves as a template for the viral RdRp, which initiates transcription by cap-snatching mechanism and generates viral mRNA. Viral mRNAs are translated producing N protein, glycoprotein precursor (which is cleaved to form G1 and G2 glycoproteins), and RdRp from the small (S), medium (M), and large (L) segment-originated mRNA, respectively.

FIGURE 2

Hantavirus life cycle. Virion binds to the cell surface membrane receptor and enters the cell via endocytosis. Once inside the cell, RNPs are released from the late endosome via pH-mediated membrane fusion. Virion-supplied RdRp is driving initial mRNA transcription which takes place in cytoplasm. Viral genomic (minus sense) RNA serves as a template for generation of mRNA utilized for protein synthesis. When sufficient amounts of the viral proteins are produced, RdRp switches to the replication mode synthesizing full length anti-genomic (plus sense) RNA, which in turn serves as a template for producing a large amount of the new full length minus sense viral RNA molecules. Newly synthesized vRNA becomes encapsidated with N protein forming ribonucleoprotein and transported into perinuclear membrane system, from where they will be transported to Golgi for initiation of virion formation. Egress takes place at the plasma membrane.

FIGURE 3

Hantavirus reassortment. Infection of one host with two different Hantavirus strains may result in reassortment. Reassortment has been shown between ANDV and SNV resulting in reassortants possessing ANDV M segment and SNV L and S segment.