Cell membrane Complex Enzyme Eukaryotic cell or cell component Microbe-host cell complex Microorganism or its component Other Other -- ion Pathway or action Protein Protein or gene Protein or gene complex Protein or protein complex Bacterial membrane or virus envelope Cell membrane Cytoplasm Eukaryotic cell or cell component Extracellular Golgi Golgi membrane Intercellular Intracellular Mitochondria Nucleocapsid/Cytoplasm Organelle Organelle -- Cell membrane Organelle -- Endoplasmic reticulum Organelle -- ER Organelle -- Golgi Organelle -- Golgi membrane Organelle -- Nucleus Organelle -- Phagolysosome Organelle -- Phagosome Organelle -- Ribosome Other Phagolysosome Phagosome Chaperone Defense, immunity protein Enzyme Enzyme activator Enzyme inhibitor Genomic S segment Infection Ligand binding or carrier Motor Nucleic acid binding Other Signal transducer Toxicity Transcription factor binding Transcription regulation Transporter Unknown IC Inferred by Curator IDA Inferred from Direct Assay IEA Inferred from Electronic Annotation IEP Inferred from Expression Pattern IGI Inferred from Genetic Interaction IMP Inferred from Mutant Phenotype IPI Inferred from Physical Interaction ISS Inferred from Sequence or Structural Similarity NAS Non-traceable Author Statement ND No biological Data available RCA inferred from Reviewed Computational Analysis TAS Traceable Author Statement NR Not Recorded Hewlett MJ, Chiu W Bunyaviridae Virion structure 1991 Gerrard SR, Nichol ST Journal of virology Characterization of the Golgi retention motif of Rift Valley fever virus G(N) glycoprotein 2002 12414959 PubMed Matsuoka Y, Chen SY, Compans RW Bunyaviridae Bunyavirus protein transport and assembly 1991 Pettersson RF, Melin L The Bunyaviridae Synthesis, assembly, and intracellular transport of Bunyaviridae membrane proteins 1996 Sanchez AJ, Vincent MJ, Nichol ST Journal of virology Characterization of the glycoproteins of Crimean-Congo hemorrhagic fever virus 2002 12072526 PubMed Papa A, Ma B, Kouidou S, Tang Q, Hang C, Antoniadis A Emerging infectious diseases Genetic characterization of the M RNA segment of Crimean Congo hemorrhagic fever virus strains, China 2002 11749748 PubMed Rwambo PM, Shaw MK, Rurangirwa FR, DeMartini JC Archives of virology Ultrastructural studies on the replication and morphogenesis of Nairobi sheep disease virus, a Nairovirus 1996 8856028 PubMed Pringle, CR The Bunyaviridae Genetics and genome segment reassortment 1996 Elliott RM, Schmaljohn CS, Collett MS Bunyaviridae Bunyaviridae genome structure and gene expression 1991 Marriott AC, Nuttall PA The Bunyaviridae Molecular biology of Nairoviruses 1996 Schmaljohn CS Field's Virology Third Edition Volume 1 Bunyaviridae: The viruses and their replication 1996 Bishop DHL The Bunyaviridae Biology and molecular biology of Bunyaviruses 1996 Schmaljohn CS, Hooper JW Fields Virology Fourth Edition Bunyaviridae: The viruses and their replication 2001 G1 and/or G2 Function: Ligand binding or carrier. The mechanisms by which members of the family Bunyaviridae gain access to the host cell's cytoplasm appear similar to those reported for many other enveloped viruses. The first step involves an interaction between cell-surface receptors and viral attachment proteins G1 and/or G2 (Schmaljohn and Hooper, 2001).(Schmaljohn2) Cell membrane receptor Function: Ligand binding or carrier. The mechanisms by which members of the family Bunyaviridae gain access to the host cell's cytoplasm appear similar to those reported for many other enveloped viruses. The first step involves an interaction between cell-surface receptors and viral attachment proteins G1 and/or G2 (Schmaljohn and Hooper, 2001). The nature of cell receptors involved in attachment has not been identified for any member of the family (Bishop, 1996).(Schmaljohn2)(Bishop) Intracellular virion Function: . Shortly after attachment, viruses in the Phlebovirus and Nairovirus genera were observed in phagocytic vacuoles. This finding suggests a mode of viral entry similar to that first described for alphaviruses in which the virus is endocytosed in coated vesicles. Acidification of the endosomes is thought to promote a conformational change in G1 and/or G2 that facilitates fusion of the viral and cell membranes, allowing the viral genome and polymerase access to the cytoplasm (Schmaljohn and Hooper, 2001).(Schmaljohn2) Fused virus Function: . Shortly after attachment, viruses in the Phlebovirus and Nairovirus genera were observed in phagocytic vacuoles. This finding suggests a mode of viral entry similar to that first described for alphaviruses in which the virus is endocytosed in coated vesicles. Acidification of the endosomes is thought to promote a conformational change in G1 and/or G2 that facilitates fusion of the viral and cell membranes, allowing the viral genome and polymerase access to the cytoplasm (Schmaljohn and Hooper, 2001).(Schmaljohn2) Uncoated virus Function: . Entry and uncoating occurs by endocytosis of virions and fusion of the viral membrane with the endosomal membrane to release the three nucleocapsids into the cell cytoplasm (Bishop, 1996). After uncoating of viral genomes, primary transcription of negative-sense vRNA to mRNA is initiated by interaction of the virion-associated polymerase (L) and the three viral RNA templates. Only ribonucleocapsids, not free RNA, can serve as transcription templates (Schmaljohn and Hooper, 2001).(Bishop)(Schmaljohn2) Ribonucleoprotein complex S viral segment Function: . Viruses in the Hantavirus and Nairovirus genera use a simple negative-sense strategy to encode N (Schmaljohn, 1996). In all nairovirus S segments examined, the viral-complementary RNA strand contains a single long open reading frame (Marriott and Nuttall, 1996).(Schmaljohn)(Marriott) N mRNA Function: . After uncoating of viral genomes, primary transcription of negative-sense vRNA to mRNA is initiated by interaction of the virion-associated polymerase (L) and the three viral RNA templates. Only ribonucleocapsids, not free RNA, can serve as transcription templates (Schmaljohn and Hooper, 2001). Synthesis of mRNA is primed by a cap-transfer mechanism analogous to that of the orthomyxoviruses, except that in the case of the Bunyaviridae it occurs in the cytoplasm, and the mRNAS do not appear to be polyadenylated (Pringle, 1996). Viral polypeptides are synthesized shortly after infection, with S and L mRNAs translated on free ribosomes, and M mRNAs translated on membrane-bound ribosomes (Schmaljohn and Hooper, 2001).(Schmaljohn2)(Pringle) N protein Function: . The N proteins of viruses in the family Bunyaviridae range in size from approximately 19 kd for bunyaviruses to 54 kd for hantaviruses and nairoviruses (Schmaljohn and Hooper, 2001). The N protein functions in formation of the individual L, M, and S nucleocapsids and therefore must interact directly with viral RNA (Elliott et al., 1991). Although not proven, it is likely that synthesis of N is required for genome replication, as described for other negative-strand RNA viruses. For these viruses, encapsidation by N seems to serve as a antitermination signal, thus allowing full-length genome synthesis (Schmaljohn and Hooper, 2001).(Schmaljohn2)(Elliott) N protein Function: . The viral ribonucleoprotein (RNP) and spike structures have been observed only on the portion of the Golgi vesicle membrane directly involved in the budding process and not on adjacent areas of the same membrane. RNPs could not be found under membranes with no spikes, suggesting that some sort of transmembranal recognition between the viral glycoproteins and the N protein is prerequisite to budding (Schmaljohn, 1996).(Schmaljohn) Antigenomic S segment Function: . For negative-strand viruses, the change from primary transcription to replication requires a switch from mRNA synthesis to synthesis of full-length cRNA templates and then vRNA. For viruses in the family Bunyaviridae the polymerase protein, acting either alone or in concert with undefined viral or cellular factors, must first function as a cap-dependent endonuclease to generate a primer for transcription of a nonencapsidated, subgenomic mRNA. At some point, the polymerase must switch to a process of independently initiating transcription at the precise 3' end of the template to produce a full-length transcript. The processes involved in making that switch from primary transcription to genome replication have not been defined completely for any member of the family. Presumably, some viral or host factor is required to signal a suppression of the transcription-termination signal responsible for generation of truncated mRNA (Schmaljohn and Hooper, 2001).Several studies on the morphology and morphogenesis of viruses in the family Bunyaviridae show that virus replication and maturation occur within the cytoplasm (Rwambo et al., 1996).(Schmaljohn2)(Rwambo et al., 1996) Genomic S segment Function: . For negative-strand viruses, the change from primary transcription to replication requires a switch from mRNA synthesis to synthesis of full-length cRNA templates and then vRNA. For viruses in the family Bunyaviridae the polymerase protein, acting either alone or in concert with undefined viral or cellular factors, must first function as a cap-dependent endonuclease to generate a primer for transcription of a nonencapsidated, subgenomic mRNA. At some point, the polymerase must switch to a process of independently initiating transcription at the precise 3' end of the template to produce a full-length transcript. The processes involved in making that switch from primary transcription to genome replication have not been defined completely for any member of the family. Presumably, some viral or host factor is required to signal a suppression of the transcription-termination signal responsible for generation of truncated mRNA (Schmaljohn and Hooper, 2001).Several studies on the morphology and morphogenesis of viruses in the family Bunyaviridae show that virus replication and maturation occur within the cytoplasm (Rwambo et al., 1996).(Schmaljohn2)(Rwambo et al., 1996) Genomic S segment Function: . Electron-dense, ribonucleoprotein structures have been observed immediately beneath the membranes where virus budding occurs. The viral nucleocapsid and spike structures were only seen on the portion of the Golgi vesicle membrane directly involved in the budding process and not on adjacent areas of the same membrane. Nucleocapsids are not found under membranes that did not have spikes, suggesting that an interaction of transmembrane regions of the viral glycoproteins and the nucleocapsids is prerequisite to budding (Bishop, 1996). At least one each of the L, M, and S ribonucleocapsids must be contained in a virion for infectivity; however equal numbers of nucleocapsids may not always be packaged in mature virions, as suggested by various reports of equimolar or nonequimolar ratios of L, M and S RNAs. Unequal complements of the ribonucleocapsids may contribute to the size differences of virions observed by electron microscopy (Schmaljohn and Hooper, 2001).(Bishop)(Schmaljohn2) Ribonucleoprotein complex M viral segment Function: . The biology of the family Bunyaviridae is dominated by the M RNA since this sub-unit encodes the genes concerned in many of the most important interactions with the host. Virulence, host range, tissue tropism, transmissibility, neutralization, hemagglutination, and membrane fusion are the principal phenotypic properties that have been attributed to M RNA gene products (Pringle, 1991). The M segment of nairoviruses is 30% to 50% larger than the M segments of members of other genera in the Bunyaviridae family and has a potential coding capacity of up to 240 kDa of protein (Papa et al., 2002).(Pringle)(Papa et al., 2002) M segment mRNA Function: . The M gene is critical for immunity and pathogenicity, as well as for vaccine development (Papa et al., 2002). Viral polypeptides are synthesized shortly after infection, with S and L mRNAs translated on free ribosomes, and M mRNAs translated on membrane-bound ribosomes (Schmaljohn and Hooper, 2001). The viral envelope glycoproteins, G1 and G2, are translated from a single mRNA complementary to vRNA (Schmaljohn and Hooper, 2001).(Papa et al., 2002)(Schmaljohn2) 85 kDa protein Function: . Viral polypeptides are synthesized shortly after infection, with S and L mRNAs translated on free ribosomes, and M mRNAs translated on membrane-bound ribosomes (Schmaljohn and Hooper, 2001). Virus protein analysis by various techniques, including pulse-chase analysis and/or reactivity with CCHF virus-specific polyclonal and antipeptide antibodies, demonstrated that a 140-kDa (which contains a mucin-like region) and a 85-kDa nonstructural protein are the precursors of the mature G2 and G1 proteins, respectively (Sanchez et al., 2002).The tetrapeptides RRLL and RKPL are immediately upstream of the cleavage site for mature G2 and G1, respectively. These are completely conserved among the predicted polyprotein sequences of all the CCHF virus strains and closely resemble the tetrapeptides that represent the major cleavage recognition sites present in the glycoprotein precursors of arenaviruses, such as Lassa fever virus (RRLL) and Pichinde virus (RKLL). These results strongly suggest that CCHF viruses (and other members of the genus Nairovirus) likely utilize the subtilase SKI-1/S1P-like cellular proteases for the major glycoprotein precursor cleavage events, as has recently been demonstrated for the arenaviruses (Sanchez et al., 2002).(Schmaljohn2)(Sanchez et al., 2002) 140 kDa protein Function: . Viral polypeptides are synthesized shortly after infection, with S and L mRNAs translated on free ribosomes, and M mRNAs translated on membrane-bound ribosomes (Schmaljohn and Hooper, 2001). Virus protein analysis by various techniques, including pulse-chase analysis and/or reactivity with CCHF virus-specific polyclonal and antipeptide antibodies, demonstrated that a 140-kDa (which contains a mucin-like region) and a 85-kDa nonstructural protein are the precursors of the mature G2 and G1 proteins, respectively (Sanchez et al., 2002).The tetrapeptides RRLL and RKPL are immediately upstream of the cleavage site for mature G2 and G1, respectively. These are completely conserved among the predicted polyprotein sequences of all the CCHF virus strains and closely resemble the tetrapeptides that represent the major cleavage recognition sites present in the glycoprotein precursors of arenaviruses, such as Lassa fever virus (RRLL) and Pichinde virus (RKLL). These results strongly suggest that CCHF viruses (and other members of the genus Nairovirus) likely utilize the subtilase SKI-1/S1P-like cellular proteases for the major glycoprotein precursor cleavage events, as has recently been demonstrated for the arenaviruses (Sanchez et al., 2002).(Schmaljohn2)(Sanchez et al., 2002) G1 protein Function: . Viral polypeptides are synthesized shortly after infection, with S and L mRNAs translated on free ribosomes, and M mRNAs translated on membrane-bound ribosomes (Schmaljohn and Hooper, 2001). All secretory proteins and membrane-bound proteins targeted to various organelles are first synthesized in the rough endoplasmic reticulum and enter the central vacuolar transport pathway. The organelles involved in this transport system include the rough and smooth endoplasmic reticulum, the cis-, medial, and trans-Golgi, the trans-Golgi network, secretory vesicles and granules, the endosomal system, lysosomes, and the plasma membrane (Matsuoka et al., 1991). G1 and G2 are cotranslationally cleaved from the primary translation product encompassing the single open reading frame in the M RNA. Each membrane protein is preceded by a separate signal sequence for targeting of the nascent chain to, and facilitating its translocation through, the ER membrane (Pettersson and Melin, 1996).(Schmaljohn2)(Matsuoka)(Pettersson) G1 protein Function: . Following synthesis, folding, glycosylation, and dimerization in the ER, G1 and G2 move to the Golgi, where further transport is arrested (Pettersson and Melin, 1996). The molecular basis for intracellular maturation depends on the transportation and retention of viral envelope glycoproteins G1 and G2 in the Golgi complex during virus replication (Rwambo et al., 1996).(Pettersson)(Rwambo et al., 1996) G1 protein Function: . Bunyavirus glycoproteins accumulate at the membranes of the Golgi apparatus prior to virus assembly, indicating that the glycoproteins may serve to direct other structural components to the site of maturation (Matsuoka et al., 1991). Members of the family Bunyaviridae lack matrix proteins; therefore, the glycoproteins (presumably the cytosolic tail region of one of the glycoproteins) are responsible for the recruitment of the remaining core elements of the virion (Gerrard and Nichol, 2002).(Matsuoka)(Gerrard et al., 2002) G2 protein Function: . Viral polypeptides are synthesized shortly after infection, with S and L mRNAs translated on free ribosomes, and M mRNAs translated on membrane-bound ribosomes (Schmaljohn and Hooper, 2001). All secretory proteins and membrane-bound proteins targeted to various organelles are first synthesized in the rough endoplasmic reticulum and enter the central vacuolar transport pathway. The organelles involved in this transport system include the rough and smooth endoplasmic reticulum, the cis-, medial, and trans-Golgi, the trans-Golgi network, secretory vesicles and granules, the endosomal system, lysosomes, and the plasma membrane (Matsuoka et al., 1991). G1 and G2 are cotranslationally cleaved from the primary translation product encompassing the single open reading frame in the M RNA. Each membrane protein is preceded by a separate signal sequence for targeting of the nascent chain to, and facilitating its translocation through, the ER membrane (Pettersson and Melin, 1996).(Schmaljohn2)(Matsuoka)(Pettersson) G2 protein Function: . Following synthesis, folding, glycosylation, and dimerization in the ER, G1 and G2 move to the Golgi, where further transport is arrested (Pettersson and Melin, 1996). The molecular basis for intracellular maturation depends on the transportation and retention of viral envelope glycoproteins G1 and G2 in the Golgi complex during virus replication (Rwambo et al., 1996).(Pettersson)(Rwambo et al., 1996) G2 protein Function: . Bunyavirus glycoproteins accumulate at the membranes of the Golgi apparatus prior to virus assembly, indicating that the glycoproteins may serve to direct other structural components to the site of maturation (Matsuoka et al., 1991). Members of the family Bunyaviridae lack matrix proteins; therefore, the glycoproteins (presumably the cytosolic tail region of one of the glycoproteins) are responsible for the recruitment of the remaining core elements of the virion (Gerrard and Nichol, 2002).(Matsuoka)(Gerrard et al., 2002) Antigenomic M segment Function: . For negative-strand viruses, the change from primary transcription to replication requires a switch from mRNA synthesis to synthesis of full-length cRNA templates and then vRNA. For viruses in the family Bunyaviridae the polymerase protein, acting either alone or in concert with undefined viral or cellular factors, must first function as a cap-dependent endonuclease to generate a primer for transcription of a nonencapsidated, subgenomic mRNA. At some point, the polymerase must switch to a process of independently initiating transcription at the precise 3' end of the template to produce a full-length transcript. The processes involved in making that switch from primary transcription to genome replication have not been defined completely for any member of the family. Presumably, some viral or host factor is required to signal a suppression of the transcription-termination signal responsible for generation of truncated mRNA (Schmaljohn and Hooper, 2001).Several studies on the morphology and morphogenesis of viruses in the family Bunyaviridae show that virus replication and maturation occur within the cytoplasm (Rwambo et al., 1996).(Schmaljohn2)(Rwambo et al., 1996) Genomic M segment Function: . For negative-strand viruses, the change from primary transcription to replication requires a switch from mRNA synthesis to synthesis of full-length cRNA templates and then vRNA. For viruses in the family Bunyaviridae the polymerase protein, acting either alone or in concert with undefined viral or cellular factors, must first function as a cap-dependent endonuclease to generate a primer for transcription of a nonencapsidated, subgenomic mRNA. At some point, the polymerase must switch to a process of independently initiating transcription at the precise 3' end of the template to produce a full-length transcript. The processes involved in making that switch from primary transcription to genome replication have not been defined completely for any member of the family. Presumably, some viral or host factor is required to signal a suppression of the transcription-termination signal responsible for generation of truncated mRNA (Schmaljohn and Hooper, 2001).Several studies on the morphology and morphogenesis of viruses in the family Bunyaviridae show that virus replication and maturation occur within the cytoplasm (Rwambo et al., 1996).(Schmaljohn2)(Rwambo et al., 1996) Genomic M segment Function: . Electron-dense, ribonucleoprotein structures have been observed immediately beneath the membranes where virus budding occurs. The viral nucleocapsid and spike structures were only seen on the portion of the Golgi vesicle membrane directly involved in the budding process and not on adjacent areas of the same membrane. Nucleocapsids are not found under membranes that did not have spikes, suggesting that an interaction of transmembrane regions of the viral glycoproteins and the nucleocapsids is prerequisite to budding (Bishop, 1996). At least one each of the L, M, and S ribonucleocapsids must be contained in a virion for infectivity; however equal numbers of nucleocapsids may not always be packaged in mature virions, as suggested by various reports of equimolar or nonequimolar ratios of L, M and S RNAs. Unequal complements of the ribonucleocapsids may contribute to the size differences of virions observed by electron microscopy (Schmaljohn and Hooper, 2001).(Bishop)(Schmaljohn2) Ribonucleoprotein complex L viral segment Function: . All L segments of viruses in the family Bunyaviridae studied to date display conventional negative-sense coding strategies (Schmaljohn, 1996). Analysis of the sizes of the genome RNA segments indicates a distinctive pattern for nairoviruses, with the L RNA segment being substantially larger (perhaps twice the size) than the L RNAs of other Bunyaviridae (Elliott et al., 1991).(Schmaljohn)(Elliott) L mRNA Function: . Viral polypeptides are synthesized shortly after infection, with S and L mRNAs translated on free ribosomes, and M mRNAs translated on membrane-bound ribosomes (Schmaljohn and Hooper, 2001).(Schmaljohn2) L protein Function: Enzyme. The L proteins of viruses in the family Bunyaviridae range in size from about 237 kd for phleboviruses to 459 kd for nairoviruses. This huge difference in protein sizes might reflect varying functional activities of the enzymes, but as yet, there are not data to support this. There are no known processing or posttranslational modifications to the L proteins (Schmaljohn and Hooper, 2001). For viruses in the family Bunyaviridae, the polymerase protein, either acting alone or in concert with undefined viral or cellular factors, must first function as a cap-dependent endonuclease to generate a primer for transcription of a nonencapsidated transcript of subgenomic length. At some point, the polymerase must switch to a process of independently initiating transcription at the precise 3' end of the template and producing an encapsidated, full-length transcript. The processes involved in making that switch from primary transcription to genome replication have not been defined completely for any member of the family Bunyaviridae. Presumably, some viral or host factor is required to signal a suppression of the transcription termination signal responsible for generation of truncated mRNA and also to prevent the addition of the capped and methylated structures to the 5' termini of the cRNAs (Schmaljohn, 1996).(Schmaljohn2)(Schmaljohn) L protein Function: Enzyme. Ribonucleoprotein structures accumulate on the cytoplasmic face of membranes that have G1 and G2 embedded into them and are exposed on the luminal side (Schmaljohn, 1996). The virion particles of the Bunyaviridae are composed of nucleocapsids containing three different RNA species (L, M, and S) complexed with the nucleocapsid protein (N) and the virion transcriptase/polymerase L. The nucleocapsids are packaged inside a lipid envelope during budding at internal cellular membranes appearing in Golgi vesicles. The lipid envelope contains two viral glycoproteins, G1 and G2. The nucleocapsids are ribonucleoprotein complexes of viral RNA and N protein (with L protein as a minor constituent) (Hewlett and Chiu, 1991).(Schmaljohn)(Hewlett) Antigenomic L segment Function: . For negative-strand viruses, the change from primary transcription to replication requires a switch from mRNA synthesis to synthesis of full-length cRNA templates and then vRNA. For viruses in the family Bunyaviridae the polymerase protein, acting either alone or in concert with undefined viral or cellular factors, must first function as a cap-dependent endonuclease to generate a primer for transcription of a nonencapsidated, subgenomic mRNA. At some point, the polymerase must switch to a process of independently initiating transcription at the precise 3' end of the template to produce a full-length transcript. The processes involved in making that switch from primary transcription to genome replication have not been defined completely for any member of the family. Presumably, some viral or host factor is required to signal a suppression of the transcription-termination signal responsible for generation of truncated mRNA (Schmaljohn and Hooper, 2001).Several studies on the morphology and morphogenesis of viruses in the family Bunyaviridae show that virus replication and maturation occur within the cytoplasm (Rwambo et al., 1996).(Schmaljohn2)(Rwambo et al., 1996) Genomic L segment Function: . For negative-strand viruses, the change from primary transcription to replication requires a switch from mRNA synthesis to synthesis of full-length cRNA templates and then vRNA. For viruses in the family Bunyaviridae the polymerase protein, acting either alone or in concert with undefined viral or cellular factors, must first function as a cap-dependent endonuclease to generate a primer for transcription of a nonencapsidated, subgenomic mRNA. At some point, the polymerase must switch to a process of independently initiating transcription at the precise 3' end of the template to produce a full-length transcript. The processes involved in making that switch from primary transcription to genome replication have not been defined completely for any member of the family. Presumably, some viral or host factor is required to signal a suppression of the transcription-termination signal responsible for generation of truncated mRNA (Schmaljohn and Hooper, 2001).Several studies on the morphology and morphogenesis of viruses in the family Bunyaviridae show that virus replication and maturation occur within the cytoplasm (Rwambo et al., 1996).(Schmaljohn2)(Rwambo et al., 1996) Genomic L segment Function: . Electron-dense, ribonucleoprotein structures have been observed immediately beneath the membranes where virus budding occurs. The viral nucleocapsid and spike structures were only seen on the portion of the Golgi vesicle membrane directly involved in the budding process and not on adjacent areas of the same membrane. Nucleocapsids are not found under membranes that did not have spikes, suggesting that an interaction of transmembrane regions of the viral glycoproteins and the nucleocapsids is prerequisite to budding (Bishop, 1996). At least one each of the L, M, and S ribonucleocapsids must be contained in a virion for infectivity; however equal numbers of nucleocapsids may not always be packaged in mature virions, as suggested by various reports of equimolar or nonequimolar ratios of L, M and S RNAs. Unequal complements of the ribonucleocapsids may contribute to the size differences of virions observed by electron microscopy (Schmaljohn and Hooper, 2001).(Bishop)(Schmaljohn2) Virion Function: . One of the earliest notable features found to distinguish members of the family Bunyaviridae from all other negative-strand viruses was that the viral particles are formed intracellularly by a budding process at smooth-surface vesicles in the Golgi area (Schmaljohn, 1996). Although the precise mechanisms of budding of enveloped viruses are not fully understood, it has been suggested that budding involves a transmembrane interaction between membrane glycoproteins and the other components of the virus in the cytoplasm, followed by pinching off from the cell surface. Upon budding, virions acquire their lipid bilayer from the host cell membrane, whereas most host cell membrane proteins are excluded from the viral particles (Matsuoka et al., 1991). At least one each of the L, M, and S ribonucleocapsids must be contained in a virion for infectivity; however equal numbers of nucleocapsids may not always be packaged in mature virions, as suggested by various reports of equimolar or nonequimolar ratios of L, M and S RNAs. Unequal complements of the ribonucleocapsids may contribute to the size differences of virions observed by electron microscopy (Schmaljohn and Hooper, 2001).The signal directing the ribonucleocapsids to the budding compartment is not known. Excess ribonucleocapsids of hantaviruses, tospovirus, and nairoviruses were found to accumulate in large cytoplasmic inclusions, suggesting that only ribonucleocapsids that interact with the envelope proteins are transported to the Golgi. It is likely that the transmembrane domains of G1 or G2 that are exposed on the cytoplasmic face of the membrane are involved in this interaction (Schmaljohn and Hooper, 2001).(Schmaljohn)(Matsuoka)(Schmaljohn2) Virion Function: . After budding into the Golgi cisternae, virions apparently are transported to the cell surface within vesicles analogous to those in the secretory pathway. The release of virus from infected cells presumably occurs when the virus-containing vesicles fuse with the cellular plasma membrane (Schmaljohn and Hooper, 2001). As with most other members of the family Bunyaviridae, release of mature virions before cell lysis is likely to occur through exocytosis (Rwambo et al., 1996).Mature Nairobi sheep disease virus (a nairovirus) was observed in smooth surface vesicles of the Golgi complex by 4 hours post infection and extracellular virus particles were observed for 10 hours after infection. Virus maturation occurred before expression of cytopathic effects that were observed at 24 hours post infection of 143B cells and at 36 hours after infection of BHK-21 cells, respectively (Rwambo et al., 1996). A reduction in host protein synthesis did not occur, even late in infection, with the phlebovirus Uukuniemi, of with the nairovirus Dugbe virus, both of which are transmitted by ticks rather than mosquitoes (Schmaljohn and Hooper, 2001).(Schmaljohn2)(Rwambo et al., 1996)