Dengue virus is an RNA virus transmitted by mosquitoes, affecting nearly 390 million people annually. The virus has four serotypes and infects host cells via attachment and internalization, leading to viral replication and maturation. Challenges for vaccine development exist due to serotype diversity, but advancements in antiviral research and vaccine development are underway.

1. DENGUE VIRUS
By S.Bhargavi

2. What is Dengue Virus
• Dengue Virus is a RNA Virus that is transmitted by a mosquito.
• This Virus is a member of Flavivirus genus.
• These Viruses effect the central nervous system and also cause Visceral
diseases in humans.
• The Dengue Virus infects nearly 390 million people each year in more then
100 countries.

3. Dengue Virus
• The Dengue Virus is 50 nm Spherical Virion that is comprised of structural proteins.
• The 3 structural proteins are capsid, membrane and the envelope also with 10.7 kb capped
RNA.
• The two mosquito vectors of Dengue Virus are Aedes albopictus / Ades aegypti and Humans.
• The 4 Dengue virus stereotypes that can cause the disease are DENV1, DENV2, DENV3,
DENV4.
• The difference in these stereotypes are 25% to 40% and these differences occur at the
amino acid level.

4. Mechanism of Dengue Virus to cause infection
• Dengue virus binds to the target cells by the help of structurally diverse
group of attachment factors.
• The bound Virions internalize with the help of Catherin which are then
transported to the endosome.
• The fusion of the viral and the host membranes occur by the structural
rearrangement of the E Protein.
• Penetration of the nucleocaspid takes place then the Viral RNA genome is
translated into the single polyprotein.

5. Mechanism of Dengue Virus to cause infection
(continued)

6. Mechanism of Dengue Virus to cause infection
(continued)
• This polyprotein is then cleaved into 3 structural and 7 non structural proteins.
• Synthesis of negative strand viral RNA occur and the leads to the synthesis of
Positive strand Viral RNA.
• The Positive strand RNA is packaged and form immature virions.
• The maturation of Virions occur in Trans Golgi network by the action of Furin
proteases.

7. Targets for antibody neutralizations
• Virion Maturity – The partially synthesized virus can also cause infection.
The cleavage of the structural proteins prM on newly synthesized virus are
required for infectivity. The uncleaved prM is recognized by the poorly
neutralizing antibodies.
• Structural heterogeneity- The Exposure of the DENV-2 to the normal
temperature of the human body can result in increase of structural
heterogeneity of the virus populations.

8. Immunity Against the Dengue Virus
• The Dengue virus infects and replicates inside the Langerhans Cells (these
cells display the antigen on their surface). Immune system gets activated and
innate immunity is triggered.
• Monocytes and macrophages ingest the virus but they also get infected.
• The infected cells release small proteins called interferon's (Part of Large
group of proteins called cytokines) they have the ability to interfere with the
viral replication and they interfere both adaptive and innate immunity.
• As the immune system fights with the infection the person experiences fever.

9. Immunity
Against the Dengue Virus (Continued )
Immune cells attacking the Dengue virus

10. Immunity Against the Dengue Virus
(continued)
• The B cells produce IgM and igG that recognize and neutralize the dengue
viral particles.
• The cytotoxic T cells recognize and kill the cells that are infected with the
virus.
• The innate immune cells activates complement system which helps the
antibodies and white blood cells to remove the virus.
• The immune system of the body thus neutralizes the dengue infection.

11. Dengue virus Vaccine
• The presence of 4 different stereotypes of Dengue viruses are a great
challenge for the synthesis of vaccine as an incompletely induced vaccine
immunity may predispose an individual to a severe disease when gets
encountered to a natural infection.
• DENVax is a live –attenuated tetravalent vaccine composed of a infectious
clone derived attenuated DENV-2 strain and three chimeric viruses that
incorporate the structural genes of other three stereotypes.

12. Advanced Research in Dengue Virus
• High throughput antiviral drugs are being discovered for the identification of
inhibitors of the fusogenic viral envelope proteins, integral membrane proteins,
protease and helicase proteins and the RNA Dependent RNA polymerases .
• Many Drugs are prepared that target the steps in DENV pathogenesis.
• Progressive discoveries are there on reducing the transmission of the DENV by
limiting the infection in the mosquito host.
• There are advances in the DENV biology in areas of host-pathogen-vector
interactions, structural biology, genetic variability, commensal biology.