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Information about Dengue Virus

Dengue virus, a member of the genus Flavivirus, is transmitted via a mosquito vector to human beings. It is a 50-nm virus with an approximately 10.7 kb, positive-sense, single-stranded, RNA genome that encodes a single large polyprotein that is subsequently cleaved into several structural and non-structural mature peptides. Research on dengue virus is important because an estimated 2.5 billion people live in areas at risk for epidemic transmission. Globally, there are an estimated 50 to 100 million cases of dengue fever (DF) and several hundred thousand cases of dengue hemorrhagic fever (DHF) per year. The average case-fatality rate of DHF ranges from 1% to 5%. The NIH/NIAID has classified dengue as a Category A priority pathogen that is regarded as a re-emerging infectious disease and a potential bioterrorist threat.

Dengue virus is made up of four similar serotypes that can cause any of four outcomes: (1) no clinical symptoms, (2) dengue fever, (3) dengue shock syndrome, and (4) dengue hemorrhagic fever. It has been observed that subsequent infection with a different serotype of the disease can result in a greater likelihood of developing dengue hemorrhagic fever due to antibody-enhanced response.

The life cycle of dengue involves endocytosis via a cell surface receptor. The virus uncoats intracellularly, where its RNA genome is translated by the host cell's ribosomes. The resulting polyprotein is subsequently cleaved by cellular and viral proteases at specific recognition sites. The viral nonstructural proteins use a negative-sense intermediate to replicate the positive-sense RNA genome, which then associates with capsid protein and is packaged into individual virions. These virions bud through the host cell membrane to obtain their lipid bilayer envelope. At this point the cycle repeats itself.

Additional research is needed, as there are a number of drug and vaccine trials in progress, but as yet, no therapeutic or preventive agent is available to the public, and the underlying mechanism of pathogenesis has not been elucidated.

Dengue Virus: Curated Genes
Virus Gene Name
(Click for gene record)
Description
Family: FlaviviridaeGenus: FlavivirusSpecies: Dengue virus type 1
DENV-WPNAURUSEQ2mp_capsidViral capsid protein; encapsidation of viral RNA
DENV-WPNAURUSEQ2mp_NS4ANonstructural protein 4A induces membrane alteration. NS4A is important for viral RNA replication (by similarity with DENV-2).
DENV-WPNAURUSEQ2mp_2K2 kDa fragment of Dengue polyprotein (signal peptide of NS4B protein)
DENV-WPNAURUSEQ2polyproteinPolyprotein precursor coded by single long ORF and processed in cell on fragments known as viral proteins
DENV-WPNAURUSEQ2mp_AnchCapstructural protein participates in encapsidation of viral RNA
DENV-WPNAURUSEQ2mp_preMMembrane glycoprotein precursor forms envelope of immature dengue virus and masks E-protein fusion with host cell membrane.
DENV-WPNAURUSEQ2mp_Mviral envelope glycoprotein; induction of apoptosis
DENV-WPNAURUSEQ2mp_EMajor envelope protein; participates in virus-host receptor binding, in fusion; induces apoptosis.
DENV-WPNAURUSEQ2mp_NS1NS1 exists as three discrete forms, that may have a different functions. The forms are a membrane-associated form, a cell surface-associated form, and a secreted form. NS1 induces an apoptosis in host; participates in virus replication. The sNS1 is immunogen secreted in blood.
DENV-WPNAURUSEQ2mp_NS2ANS2A protein
DENV-WPNAURUSEQ2mp_NS2BCo-factor of viral serin protease complex NS2B-NS3.
DENV-WPNAURUSEQ2mp_NS3protease activity; helicase; triphosphatase; induction of apoptosis
DENV-WPNAURUSEQ2mp_NS4BInterferon inhibitor; participant in viral RNA replication via NS3 interaction
DENV-WPNAURUSEQ2mp_NS5RNA-directed RNA polymerase; replication complex
Family: FlaviviridaeGenus: FlavivirusSpecies: Dengue virus type 2
DENV-16681SEQ2polyproteinPolyprotein precursor coded by single long ORF and processed in cell on fragments known as viral proteins
DENV-16681SEQ2mp_anchCAnchored capsid protein
DENV-16681SEQ2mp_virCViral RNA genome packaging
DENV-16681SEQ2mp_prMEnvelope protein of immature virion with role in viral assembly and in protection of protein E from fusion.
DENV-16681SEQ2mp_MVirus-host interaction; cell cycle arrest; induction of apoptosis
DENV-16681SEQ2mp_EMajor envelope protein; participant in replication, in virus-host receptor binding, in fusion, in virus propagation.
DENV-16681SEQ2mp_NS1Virus-host interaction, viral replication; induction of apoptosis; immunogenic secreted protein.
DENV-16681SEQ2mp_NS2AInhibitor of IFN
DENV-16681SEQ2mp_NS2BCo-factor of viral serine protease complex NS2B-NS3
DENV-16681SEQ2mp_NS3Protease; helicase; triphosphatase
DENV-16681SEQ2mp_NS4AInhibitor of IFN; component of viral replication complex
DENV-16681SEQ2mp_2K2 kDa fragment of Dengue polyprotein (signal peptide)
DENV-16681SEQ2mp_NS4BParticipant in RNA replication; inhibitor of IFN
DENV-16681SEQ2mp_NS5RNA-directed RNA polymerase; 5'-methyltransferase activity
Family: FlaviviridaeGenus: FlavivirusSpecies: Dengue virus type 3
DENV-D3HIS20001266Capsid proteinMature capsid protein with role in viral RNA genome packaging
DENV-D3HIS20001266Membrane glicoprotein precursorEnvelope protein of immature virion with role in viral assembly and in protection of protein E from fusion with host cell membrane
DENV-D3HIS20001266Nonstructural protein NS4AParticipant of viral RNA replication, potential inhibitor of IFN (by similarity with DENV-2)
DENV-D3HIS200012662K peptide2 kDa fragment of Dengue polyprotein (signal peptide)
DENV-D3HIS20001266polyproteinPolyprotein precursor coded by single long ORF and processed in cell on fragments known as viral proteins
DENV-D3HIS20001266Anchored capsid proteinAnchored capsid protein
DENV-D3HIS20001266Membrane glycoproteinMembrane glycoprotein forms envelope of mature dengue virus; participates in virus-host interaction and in apoptosis of cell
DENV-D3HIS20001266Envelope proteinMajor envelope protein involved in virus-host receptor binding, in fusion with host cell membrane.
DENV-D3HIS20001266Nonstructural protein NS1Secreted protein with immunogenic function
DENV-D3HIS20001266Nonstructural protein NS2ANS2A protein; viral immunogenic factor
DENV-D3HIS20001266Nonstructural protein NS2BCo-factor of viral serine protease complex NS2B-NS3
DENV-D3HIS20001266Nonstructural protein NS3Serine protease activity in complex with viral NS2B protein; NTP/helicase activity; component of viral replication complex
DENV-D3HIS20001266Nonstructural protein NS4BParticipant in viral RNA replication; potential IFN inhibitor (by similarity with other types of dengue virus)
DENV-D3HIS20001266Nonstructural protein NS5RNA-directed RNA polymerase; 5`-methyltransferase activity ; main component of viral replication complex
Family: FlaviviridaeGenus: FlavivirusSpecies: Dengue virus type 4
DENV-814669SEQ4polyprotein precursorPolyprotein precursor coded by single long ORF and processed in cell on fragments known as viral proteins
DENV-814669SEQ4mp_anchored capsid _anchC_ proteinAnchored capsid protein
DENV-814669SEQ4mp_virion capsid _virC_ proteinViral RNA genome packaging
DENV-814669SEQ4mp_membrane precursor _prM_ proteinMembrane glycoprotein precursor forms envelope of immature dengue virus and masks E-protein fusion with host cell membrane
DENV-814669SEQ4mp_membrane _M_ proteinviral envelope glycoprotein of mature virus; induction of apoptosis
DENV-814669SEQ4mp_envelope _E_ proteinMajor envelope viral protein involved in host-virus receptor binding, in fusion with infected host cell and in virus propagation.
DENV-814669SEQ4mp_NS1 proteinGlycosylated secreted protein circulating in blood after infection; immunogen. Three forms of NS1 with different functions are described for DENV-1 NS1 protein (see VBRC data)
DENV-814669SEQ4mp_NS2A proteinViral immunogenic factor
DENV-814669SEQ4mp_NS2B proteinViral protease cofactor NS2B (40 aa of NS2B and 184 N- terminus aa of NS3 form a two- component serine protease complex)
DENV-814669SEQ4mp_NS3 proteinProtease; helicase; triphosphatase
DENV-814669SEQ4mp_NS4A proteinParticipant in viral RNA replication, potential inhibitor of IFN (by similarity with DENV-2)
DENV-814669SEQ4mp_2K protein2 kDa fragment of Dengue polyprotein, signal peptide (by similarity with DENV-2 2K protein)
DENV-814669SEQ4mp_NS4B proteinParticipant in viral RNA replication; potential IFN inhibitor
DENV-814669SEQ4mp_NS5 proteinRNA-directed RNA polymerase; 5`-methyltransferase activity; main component of viral replication complex


Dengue Virus Gene Map
Modified from Field's Virology, 5th ed. vol.1, ch.33, p.1107
polyprotein anchored capsid protein (C) prM (M) protein E protein NS1 protein NS2a NS2b NS3 NS4a protein 2K protein NS4b NS5 capsid protein (C) M NS2Aa NS3 (cleaved)
gene map legend
Dengue virus genome structure, polyprotein processing, and cleavage products. The top row is a representation of the initial polyprotein translation product. The middle and bottom rows show the peptide precursors and mature protein products generated by the proteolytic processing cascade. Structural proteins are dark red and nonstructural proteins are white. The arrows indicate protease cleavage sites and are colored according to the particular protease responsible for cleavage (as indicated in the legend).
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