Introduction

Taxonomic Structure of the Family

Family	Bunyaviridae
Genus	Bunyavirus
Genus	Hantavirus
Genus	Nairovirus
Genus	Phlebovirus
Genus	Tospovirus

Virion Properties

Morphology

Morphological properties vary among viruses in each of the five genera; however, virions generally are spherical or pleomorphic, 80-120  nm in diameter, and display surface glycoprotein projections of 5-10  nm which are embedded in a lipid bilayered envelope approximately 5  nm thick. Virion envelopes are usually derived from cellular Golgi membranes, or on occasion, from cell surface membranes. Viral ribonucleocapsids are 2-2.5  nm in diameter, 200-3,000  nm in length, and display helical symmetry (Fig. 1).

Physicochemical and Physical Properties

The virion Mr is 300-400 10⁶ and has an S_20W of 350-500S. Virion buoyant densities in sucrose and CsCl are 1.16-1.18 and 1.20-1.21  g/cm³, respectively. Virions are sensitive to heat, lipid solvents, detergents, and formaldehyde.

Nucleic Acid

The viral genome comprises 3 unique molecules of negative or ambisense ssRNA, designated L (large), M (medium) and S (small), which total 11-19  kb (Table 1). The terminal nucleotides of each genome RNA segment are base-paired forming non-covalently closed, circular RNAs (and ribonucleocapsids). The terminal nucleotide sequences of genome segments are conserved among viruses in each genus but are different from those of viruses in other genera. The genome RNAs are not modified at their 5-ends. The Mr of the genome ranges from 4.8-8 10⁶ and this constitutes 1-2% of the virion by weight. Viral messenger RNAs (mRNAs) are not polyadenylated and are truncated relative to the genome RNAs at the 3-termini. mRNAs have 5-methylated caps and 10-18 non-templated nucleotides which are derived from host-cell mRNAs.

Proteins

All viruses have four structural proteins, 2 external glycoproteins (G1, G2), a nucleocapsid protein (N), and a large (L) transcriptase protein. Non-structural proteins of generally unknown function are expressed from the S segments of bunyaviruses, phleboviruses, and tospoviruses, and from the M segments of bunyaviruses, nairoviruses, tospoviruses and some phleboviruses. Hantaviruses do not apparently encode non-structural proteins. Proteins encoded by each of the genome segments of viruses in each genus of the family are listed in Table 2.

Lipids

Virions contain 20-30% lipids by weight. Lipids are derived from the membranes where viruses mature and include phopholipids, sterols, fatty acids and glycolipids.

Carbohydrates

Virions are composed of 2-7% carbohydrate by weight. Asparagine-linked sugars on the G1 and G2 proteins are largely of the high mannose type when viruses are grown in vertebrate cells.

Genome Organization and Replication

The genome organization of the different genera is shown in Figure 2. For all viruses, the L, M and S genome segments encode, respectively, the viral RNA polymerase (L protein), envelope glycoproteins (G1 and G2) and nucleocapsid protein (N) in the virus-complementary sense RNA. The L protein is encoded in the complementary mRNA. A single, continuous ORF in the M RNA encodes the glycoproteins, and the primary gene product is co-translationally cleaved (except for nairoviruses) to give mature G1 and G2. Hantaviruses and Uukuniemi-like phleboviruses encode no additional proteins in their M genome segments. Bunyaviruses and other phleboviruses encode a nonstructural protein (NSm) in the virion-complementary sense RNA. Nairoviruses encode at least two nonstructural proteins which are precursors to the viral glycoproteins. Tospoviruses encode a NSm protein in an ambisense ORF at the 5-end of virion-sense RNA. Hantaviruses and nairoviruses encode no additional proteins in their S genome segments. Bunyaviruses encode a nonstructural protein (NSs) in an overlapping ORF to that encoding N in the 3-half of the virion-sense S RNA. Phleboviruses and tospoviruses encode a NSs protein in an ambisense ORF in the 5-half of virion-sense S RNA. There is no evidence to suggest that the nonstructural proteins encoded by viruses in different genera are isofunctional even though they have been given similar names.

All stages of replication occur in the cytoplasm. The principal stages of replication are:

1.	Attachment, mediated by an interaction of one or both of the integral viral envelope proteins with as yet unidentified host receptors.
2.	Entry and uncoating, by endocytosis of virions and fusion of viral membranes with endosomal membranes.
3.	Primary transcription, i.e., the synthesis of mRNA species complementary to the genome templates by the virion-associated polymerase using host cell-derived capped primers (Fig. 3).
4.	Translation of primary L and S segment mRNAs by free ribosomes; translation of M segment mRNAs by membrane-bound ribosomes and primary glycosylation of nascent envelope proteins. Co-translational cleavage of a precursor to yield G1 and G2, and for some viruses, NSm.
5.	Synthesis and encapsidation of antigenome RNA to serve as templates for genomic RNA or, in some cases, for subgenomic mRNA.
6.	Genome replication (Fig. 3).
7.	Secondary transcription, i.e., the amplified synthesis of the mRNA species and ambisense transcription.
8.	Morphogenesis, including accumulation of G1 and G2 in the Golgi, terminal glycosylation, acquisition of modified host membranes, generally by budding into the Golgi cisternae, but budding at the cell surface has been observed with Rift Valley fever virus (Phlebovirus) in rat hepatocytes and Sin Nombre virus (Hantavirus) in polarised epithelial cells.
9.	Fusion of cytoplasmic vesicles with the plasma membrane and release of mature virions.

Antigenic Properties

One or both of the envelope glycoproteins display hemagglutinating and neutralizing antigenic determinants. Complement fixing antigenic determinants are principally associated with nucleocapsid protein.

Biological Properties

Viruses in the genera Bunyavirus, Nairovirus and Phlebovirus are capable of alternately replicating in vetebrates and arthropods, and generally are cytolytic for their vertebrate hosts, but cause little or no cytopathogenicity in their invertebrate hosts. Different viruses are transmitted by mosquitoes, ticks, phlebotomine flies, and other arthropod vectors. Some viruses display a very narrow host range, especially for arthropod vectors. No arthropod vector has been demonstrated for hantaviruses. Tospoviruses can be transmitted by thrips between plants and are capable of replicating in both thrips and plants. Transovarial and venereal transmission have been demonstrated for some mosquito-borne viruses. Aerosol infection occurs in certain situations or is the principal means of transmission for some viruses, particularly hantaviruses. In some instances, avian host and/or vector movements may result in virus dissemination. Some viruses cause a reduction in host-cell protein synthesis in vertebrate cells. Hantaviruses cause no detectable reduction in host macromolecular synthesis and routinely establish persistent, non-cytolytic infections in susceptible mammalian host cells, a finding consistent with their non-pathogenic persistence in their natural rodent hosts. In natural infections of mammals, viruses are often targeted to a particular organ or cell type. Some viruses induce cell fusion at low pH. Some members have ion-dependent hemagglutinating activity. Genetic reassortment has been demonstrated for certain members both in vitro and in vivo.