Dynein-Dependent Transport of the Hantaan Virus Nucleocapsid Protein to the Endoplasmic Reticulum-Golgi Intermediate Compartment

Ramanathan, Harish N.; Chung, Donghoon; Plane, Steven J.; Sztul, Elizabeth; Chu, Yong-Kyu; Guttieri, Mary C.; McDowell, Michael M.; Ali, Georgia D.; Jonsson, Colleen B.

doi:10.1128/jvi.00418-07

Cited by 77 publications

(108 citation statements)

References 83 publications

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“…The orientation of the left panel is identical to that in A and is rotated 180°from the right panel, which is identical in the orientation of C. Conserved surface residues forming the acidic (red) and basic (blue) surfaces are indicated. Point mutations of Arg 22 and Lys 26 had a dramatic effect on the antibody recognition of the N protein in vivo. Table 1) showed similar ␣-helical CD spectra.…”

Section: Circular Dichroism Spectroscopy Of N 1-74mentioning

confidence: 99%

“…3A). On the same face of the hydrophobic heptad, there is another seven-residue repeat, in this case, composed of polar residues on helix ␣ 1 (Gln 8 , Glu 15 , Arg 22 , and Glu 29 ) (Fig. 2B), which are invariant among the hantaviruses (supplemental Fig.…”

Section: Nmr Structure Determination Of N 1-74mentioning

confidence: 99%

“…-Point mutations were introduced in the basic (Arg 22 , Lys 24 , Lys 26 , and Arg 47 ) and acidic (Glu 33 and Asp 38 ) surfaces. In addition, we mutated Gln 23 , which is near the basic region, and Pro 36 , which is near the acidic region.…”

Section: Circular Dichroism Spectroscopy Of N 1-74mentioning

confidence: 99%

“…We used CD spectroscopy to confirm that mutations did not alter the coiled coil structure of the N (residues 1-74 of the N protein) domain. However, immunocytochemistry showed that despite the N protein being present throughout the cytoplasm, a monoclonal antibody only recognized the Arg 22 and Lys 26 mutants when nucleocapsids are associated with the Golgi, the site of viral assembly and maturation. We propose that the conserved surface residues Arg 22 and Lys 26 are important in the proper conformation or molecular recognition of the N protein.…”

mentioning

confidence: 99%

“…It is highly conserved and is the most abundant viral protein, and it plays important roles in viral encapsidation, RNA packaging, and host-pathogen interaction (16). The N protein binds to viral proteins (16), host proteins (17)(18)(19)(20)(21)(22)(23), and viral RNA (24 -28). The self-association of the N protein into trimers was shown by gradient fractionation and chemical cross-linking (29).…”

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confidence: 99%

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NMR Structure of the N-terminal Coiled Coil Domain of the Andes Hantavirus Nucleocapsid Protein

Wang

Boudreaux

Estrada

et al. 2008

Journal of Biological Chemistry

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The hantaviruses are emerging infectious viruses that in humans can cause a cardiopulmonary syndrome or a hemorrhagic fever with renal syndrome. The nucleocapsid (N) is the most abundant viral protein, and during viral assembly, the N protein forms trimers and packages the viral RNA genome. Here, we report the NMR structure of the N-terminal domain (residues 1-74, called N 1-74 ) of the Andes hantavirus N protein. N 1-74 forms two long helices (␣ 1 and ␣ 2 ) that intertwine into a coiled coil domain. The conserved hydrophobic residues at the helix ␣ 1 -␣ 2 interface stabilize the coiled coil; however, there are many conserved surface residues whose function is not known. Site-directed mutagenesis, CD spectroscopy, and immunocytochemistry reveal that a point mutation in the conserved basic surface formed by Arg 22 or Lys 26 lead to antibody recognition based on the subcellular localization of the N protein. Thus, Arg 22 and Lys 26 are likely involved in a conformational change or molecular recognition when the N protein is trafficked from the cytoplasm to the Golgi, the site of viral assembly and maturation.Hantaviruses can cause two emerging infectious diseases known as the hantavirus cardiopulmonary syndrome (HCPS) 3 and the hantavirus hemorrhagic fever with renal syndrome (1). Annually, there are over 150,000 cases of hantaviral infections reported world wide (2). Rodents are the primary reservoir of hantaviruses, and humans are normally infected by inhalation of aerosol contaminated with the excreta of infected rodents. The first reported cases of HCPS in North America (3) was caused by a novel hantaviral species (4, 5), the Sin Nombre virus, and had an initial mortality rate of 78%. HCPS has since been reported throughout the United States with a current mortality rate of 35% when correctly diagnosed (6). The major cause of HCPS in South America is the Andes virus, and person-to-person transmission of the Andes virus was reported in Argentina and Chile (7). Hantaviruses are known to invade and replicate primarily in endothelial cells, including the endothelium of vascular tissues lining the heart (8 -10).The genome of hantaviruses consists of three negativestranded RNAs, which encode the nucleocapsid (N) protein, two integral membrane glycoproteins (G1 and G2), and an RNAdependent RNA polymerase (L protein). The N protein is highly immunogenic (11, 12) and elicits a strong immune response, which confers protection in mice (13-15). It is highly conserved and is the most abundant viral protein, and it plays important roles in viral encapsidation, RNA packaging, and host-pathogen interaction (16). The N protein binds to viral proteins (16), host proteins (17-23), and viral RNA (24 -28). The self-association of the N protein into trimers was shown by gradient fractionation and chemical cross-linking (29). Deletion mapping identified that regions at the N and C termini are important in N-N interaction (29 -31), and a model of trimerization was proposed based on the head-to-head and tail-to-tail association of the...

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Section: Circular Dichroism Spectroscopy Of N 1-74mentioning

confidence: 99%

Section: Nmr Structure Determination Of N 1-74mentioning

confidence: 99%

Section: Circular Dichroism Spectroscopy Of N 1-74mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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NMR Structure of the N-terminal Coiled Coil Domain of the Andes Hantavirus Nucleocapsid Protein

Wang

Boudreaux

Estrada

et al. 2008

Journal of Biological Chemistry

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Bunyaviridae

Taylor¹,

Altamura²,

Schmaljohn³

2009

Encyclopedia of Life Sciences

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The family Bunyaviridae is a large and diverse group of enveloped viruses with ribonucleic acid (RNA) genomes. The family consists of over 300 species that are divided into 5 genera. All bunyavirus genomes are comprised of three negative‐sense RNA segments, but they differ in their coding strategies to generate the structural and nonstructural proteins required for replication. Viruses are transmitted by infected vectors that include mosquitoes, phlebotomine flies, ticks and rodents. Bunyaviruses are distributed worldwide and are responsible for a variety of illnesses in human hosts ranging from mild to haemorrhagic fevers or fatal encephalitis. Thus, bunyaviruses are important infectious agents and vector control, precautionary measures, and education are needed to prevent future outbreaks in endemic areas. Key Concepts Bunyavirus replication occurs in the cytoplasm via a viral RNA‐dependent RNA polymerase. All bunyavirus genomes consist of three negative‐sense RNA segments that encode for structural and/or nonstructural proteins. Structural proteins are required for replication and nonstructural proteins generally play a role in evading host cellular responses. Vectors that transmit bunyaviruses to humans include mosquitoes, phelobotomine flies, ticks and rodents. Symptoms of bunyavirus infection include mild febrile illness, haemorrhagic fever and encephalitis. Bunyaviruses can be found worldwide, so precautionary measures should be taken when travelling to endemic areas.

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