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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.
| Virus | Gene Name (Click for gene record) |
Description |
|---|---|---|
| Family: FlaviviridaeGenus: FlavivirusSpecies: Dengue virus type 1 | ||
| DENV-WPNAURUSEQ2 | mp_capsid | Viral capsid protein; encapsidation of viral RNA |
| DENV-WPNAURUSEQ2 | mp_NS4A | Nonstructural protein 4A induces membrane alteration. NS4A is important for viral RNA replication (by similarity with DENV-2). |
| DENV-WPNAURUSEQ2 | mp_2K | 2 kDa fragment of Dengue polyprotein (signal peptide of NS4B protein) |
| DENV-WPNAURUSEQ2 | polyprotein | Polyprotein precursor coded by single long ORF and processed in cell on fragments known as viral proteins |
| DENV-WPNAURUSEQ2 | mp_AnchCap | structural protein participates in encapsidation of viral RNA |
| DENV-WPNAURUSEQ2 | mp_preM | Membrane glycoprotein precursor forms envelope of immature dengue virus and masks E-protein fusion with host cell membrane. |
| DENV-WPNAURUSEQ2 | mp_M | viral envelope glycoprotein; induction of apoptosis |
| DENV-WPNAURUSEQ2 | mp_E | Major envelope protein; participates in virus-host receptor binding, in fusion; induces apoptosis. |
| DENV-WPNAURUSEQ2 | mp_NS1 | NS1 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-WPNAURUSEQ2 | mp_NS2A | NS2A protein |
| DENV-WPNAURUSEQ2 | mp_NS2B | Co-factor of viral serin protease complex NS2B-NS3. |
| DENV-WPNAURUSEQ2 | mp_NS3 | protease activity; helicase; triphosphatase; induction of apoptosis |
| DENV-WPNAURUSEQ2 | mp_NS4B | Interferon inhibitor; participant in viral RNA replication via NS3 interaction |
| DENV-WPNAURUSEQ2 | mp_NS5 | RNA-directed RNA polymerase; replication complex |
| Family: FlaviviridaeGenus: FlavivirusSpecies: Dengue virus type 2 | ||
| DENV-16681SEQ2 | polyprotein | Polyprotein precursor coded by single long ORF and processed in cell on fragments known as viral proteins |
| DENV-16681SEQ2 | mp_anchC | Anchored capsid protein |
| DENV-16681SEQ2 | mp_virC | Viral RNA genome packaging |
| DENV-16681SEQ2 | mp_prM | Envelope protein of immature virion with role in viral assembly and in protection of protein E from fusion. |
| DENV-16681SEQ2 | mp_M | Virus-host interaction; cell cycle arrest; induction of apoptosis |
| DENV-16681SEQ2 | mp_E | Major envelope protein; participant in replication, in virus-host receptor binding, in fusion, in virus propagation. |
| DENV-16681SEQ2 | mp_NS1 | Virus-host interaction, viral replication; induction of apoptosis; immunogenic secreted protein. |
| DENV-16681SEQ2 | mp_NS2A | Inhibitor of IFN |
| DENV-16681SEQ2 | mp_NS2B | Co-factor of viral serine protease complex NS2B-NS3 |
| DENV-16681SEQ2 | mp_NS3 | Protease; helicase; triphosphatase |
| DENV-16681SEQ2 | mp_NS4A | Inhibitor of IFN; component of viral replication complex |
| DENV-16681SEQ2 | mp_2K | 2 kDa fragment of Dengue polyprotein (signal peptide) |
| DENV-16681SEQ2 | mp_NS4B | Participant in RNA replication; inhibitor of IFN |
| DENV-16681SEQ2 | mp_NS5 | RNA-directed RNA polymerase; 5'-methyltransferase activity |
| Family: FlaviviridaeGenus: FlavivirusSpecies: Dengue virus type 3 | ||
| DENV-D3HIS20001266 | Capsid protein | Mature capsid protein with role in viral RNA genome packaging |
| DENV-D3HIS20001266 | Membrane glicoprotein precursor | Envelope protein of immature virion with role in viral assembly and in protection of protein E from fusion with host cell membrane |
| DENV-D3HIS20001266 | Nonstructural protein NS4A | Participant of viral RNA replication, potential inhibitor of IFN (by similarity with DENV-2) |
| DENV-D3HIS20001266 | 2K peptide | 2 kDa fragment of Dengue polyprotein (signal peptide) |
| DENV-D3HIS20001266 | polyprotein | Polyprotein precursor coded by single long ORF and processed in cell on fragments known as viral proteins |
| DENV-D3HIS20001266 | Anchored capsid protein | Anchored capsid protein |
| DENV-D3HIS20001266 | Membrane glycoprotein | Membrane glycoprotein forms envelope of mature dengue virus; participates in virus-host interaction and in apoptosis of cell |
| DENV-D3HIS20001266 | Envelope protein | Major envelope protein involved in virus-host receptor binding, in fusion with host cell membrane. |
| DENV-D3HIS20001266 | Nonstructural protein NS1 | Secreted protein with immunogenic function |
| DENV-D3HIS20001266 | Nonstructural protein NS2A | NS2A protein; viral immunogenic factor |
| DENV-D3HIS20001266 | Nonstructural protein NS2B | Co-factor of viral serine protease complex NS2B-NS3 |
| DENV-D3HIS20001266 | Nonstructural protein NS3 | Serine protease activity in complex with viral NS2B protein; NTP/helicase activity; component of viral replication complex |
| DENV-D3HIS20001266 | Nonstructural protein NS4B | Participant in viral RNA replication; potential IFN inhibitor (by similarity with other types of dengue virus) |
| DENV-D3HIS20001266 | Nonstructural protein NS5 | RNA-directed RNA polymerase; 5`-methyltransferase activity ; main component of viral replication complex |
| Family: FlaviviridaeGenus: FlavivirusSpecies: Dengue virus type 4 | ||
| DENV-814669SEQ4 | polyprotein precursor | Polyprotein precursor coded by single long ORF and processed in cell on fragments known as viral proteins |
| DENV-814669SEQ4 | mp_anchored capsid _anchC_ protein | Anchored capsid protein |
| DENV-814669SEQ4 | mp_virion capsid _virC_ protein | Viral RNA genome packaging |
| DENV-814669SEQ4 | mp_membrane precursor _prM_ protein | Membrane glycoprotein precursor forms envelope of immature dengue virus and masks E-protein fusion with host cell membrane |
| DENV-814669SEQ4 | mp_membrane _M_ protein | viral envelope glycoprotein of mature virus; induction of apoptosis |
| DENV-814669SEQ4 | mp_envelope _E_ protein | Major envelope viral protein involved in host-virus receptor binding, in fusion with infected host cell and in virus propagation. |
| DENV-814669SEQ4 | mp_NS1 protein | Glycosylated 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-814669SEQ4 | mp_NS2A protein | Viral immunogenic factor |
| DENV-814669SEQ4 | mp_NS2B protein | Viral protease cofactor NS2B (40 aa of NS2B and 184 N- terminus aa of NS3 form a two- component serine protease complex) |
| DENV-814669SEQ4 | mp_NS3 protein | Protease; helicase; triphosphatase |
| DENV-814669SEQ4 | mp_NS4A protein | Participant in viral RNA replication, potential inhibitor of IFN (by similarity with DENV-2) |
| DENV-814669SEQ4 | mp_2K protein | 2 kDa fragment of Dengue polyprotein, signal peptide (by similarity with DENV-2 2K protein) |
| DENV-814669SEQ4 | mp_NS4B protein | Participant in viral RNA replication; potential IFN inhibitor |
| DENV-814669SEQ4 | mp_NS5 protein | RNA-directed RNA polymerase; 5`-methyltransferase activity; main component of viral replication complex |