Introduction to Dengue Virus (virology).pptx

Dengue virus

1. Dengue virus 1 Dengue Virus

2. What is Dengue virus? Spherical Enveloped Virion 40-50 nm in diameter Single stranded positive sense RNA genome Genome is surrounded by an icosahedral nucleocapsid . Genome size is 11kb. Immune cells are targeted by DV Acute infectious Viral disease, Break bone Fever. Blood borne disease Spread by Mosquitos (Aedes Agypti ) Fatality rate as high as 40-50% Four serotypes, DV1, DV2, DV3, DV4 2

3. Classification Group: IV+ssRNA Order: UNASSIGNED FAMILY: FLAVIVIRIDAE GENUS: FLAVIVIRUS SPECIES: DENGUE VIRUS 3

4. Classification is based on the Baltimore Classification The  Baltimore classification , developed by David Baltimore Virus classification  system that groups  viruses  into families Depending on their type of genome (DNA, RNA, single-stranded, double-stranded ) and their method of replication. In case of dengue virus IV+ssRNA 4

5. Epidemiology Dengue fever has become more common since 1980’s. By 1990’s it became 2 nd most important mosquito borne viral disease after Malaria with around 40 million case of DF. First confirmed outbreak was in 1994 in Pakistan Sudden annual epidemic rise in 2005 in Karachi. Average annual number of dengue fever (DF) and dengue hemorrhagic fever (DHF) cases reported to WHO and average annual number of countries reporting dengue. 5

6. 6

7. Virus Structure and Components Structure of the dengue virus is roughly spherical With a diameter of approximately 50 nm. The core of the virus is the nucleocapsid , a structure that is made of the viral genome along with C proteins. The nucleocapsid is surrounded by a membrane, the viral envelope, Envelope, a lipid bilayer that is taken from the host. 7

8. Capsid Capsid of the dengue virus is icosahedral in symmetry Mature dengue virus capsid is a highly basic protein of 12 kDa that forms homodimers Envelope Dengue virus is an enveloped virus Envelope of dengue virus is derived from the host cytoplasm   Envelope proteins (E) on the surface of the dengue virus that allow it to interact with host cells 53 KDa , glycoprotein 8

9. 9

10. Genome Single stranded, linear, + ve sense, RNA, 11kb The genome encodes only 10 proteins. Out of which 3 are structural proteins and 7 are non structural proteins. The 3 structural proteins (C, M and E) form the coat of the virus. The seven non structural proteins ( NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5) 10

11. 11

12. Processes in Dengue Virus Attachment to the cell surface Entry into the cytoplasm Translation Replication Assembly of virion Release from the cell 12

13. Attachment and Entry Dengue virus E envelope protein binds to a cellular receptor, the exact nature of the cellular receptor has not been fully elucidated DENV undergoes endocytosis Acidification of the endosome leads to a conformational change of E protein Uncoating occurs in the cytoplasm Genome enters the cytoplasm and moves toward the endoplasmic reticulum 13

14. Translation and Replication Genome is + ve sense RNA, no transcription occurs The viral genome act as mRNA and is translated into polyprotein at rough endoplasmic reticulum Viral and cellular proteases are responsible Viral replication occurs in two steps First the positive-mRNA is copied to negative sense mRNA 14

15. Which, in turn, serves as a template for the synthesis of multiple strands of positive sense RNAs Then the positive-sense RNA can be used for translation As RdRNA polymerase is synthesized RNA replication commence 15 + ve mRNA - ve mRNA + ve mRNA

16. Assembly and Release Virus assembly occurs at the endoplasmic reticulum (ER) membrane C protein and vRNA are enveloped by the ER membrane and glycoproteins to form immature virus particles Immature virus particles are transported through the secretory pathway, and in the acidic environment of the trans-Golgi network (TGN) M protein drives maturation of the virus Mature virus is released from the cell 16

17. Structural and enzymatic proteins 17

18. E-protein/M-protein E-protein, found as a dimer on the surface of the mature viral particle important in the initial attachment of this particle to the host cell membrane protein(M), important in the formation and maturation of the viral particle mature DENV virion consists of 180 copies each of the E protein and M protein Virion, exposed to low pH, conformational change in the E protein, form E homodimers 18

19. 19

20. 20

21. Disease caused by Dengue virus Immune cells are targeted by Dengue virus Then spread in lymphatic system Dengue virus causes dengue fever A person develops viremia Condition in which there is a high level of the dengue virus in the blood Common names for dengue fever include breakbone fever and dandy fever 21

22. Number of platelets reduced in Dengue infection Symptoms may include severe headache, muscle, joint, and bone pain, nausea, vomiting, eye pain, rashes Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are the severe forms People with weakened immune systems, second or subsequent dengue infection are believed to be at greater risk for developing dengue hemorrhagic fever. 22

23. 23

24. Dengue hemorrhagic fever (DHF) Severe and fatal form of dengue fever. It can appear as a benign infection as well but can quickly develop into life threatening illness. It has 3 phases: The febrile phase The critical phase The reabsorption phase Symptoms, severe and continuous pain in abdomen, bleeding from the nose, mouth and gums, frequent vomiting with or without blood 24

25. Dengue shock syndrome (DSS) Shock can cause death within 12 to 24 hours but patients can recover by appropriate medical treatment. Dengue haemorrhage fever changes to dengue shock syndrome after 3 to 5 days. It is characterized by bleeding that appear as tiny spots of blood on skin and larger patches of blood under the skin and minor injuries may cause bleeding. Symptoms, hypotension 25

26. 26

27. Transmission Vector borne virus, spread through arthropods Dengue virus is transmitted through mosquitoes Infected female Aedes aegypti bites the person Lives in the gut of A. aegypti Infected person, carrier of dengue virus The incubation period is 3 to 14 days Human-to-mosquito-to-human cycle of transmission 27

28. 28

29. Prevention and Control Prevention depends on control and protection from the bites of the mosquito that transmits it.  Primary method, eliminating A. aegypti  habitats Reducing open collections of water Application of insect repellent Use endotoxin-producing bacteria ( Bacillus thuringiensis  serotype H-14) as biological control A pplication of larvicidal insecticides, as chemical control 29

30. Treatment   No specific medicine to treat dengue infection Should use pain relievers with  acetaminophen Avoid medicines with aspirin Non-steroidal anti-inflammatory drugs should be avoided They increase the bleeding Patients may receive paracetamol preparations to deal with these symptoms if dengue is suspected 30

31. Vaccine No effective vaccine is currently available Several vaccines are under development by private and public researchers Vaccine must immunize against all four types to be effective Vaccination against only one serotype could possibly lead to severe dengue hemorrhagic shock (DHS) when infected with another serotype due to antibody-dependent enhancement In late 2015 and early 2016, the first dengue vaccine, Dengvaxia (CYD-TDV) by Sanofi Pasteur, was registered 31

32. References https://en.wikipedia.org/wiki/Dengue_virus https://www.webmd.com/a-to-z-guides/dengue-fever-reference http://www.denguevirusnet.com/dengue-virus.html https://www.nature.com/scitable/topicpage/dengue-viruses-22400925 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759171/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856379/ 32

33. 33