This lecture is presented by our volunteer Sajid Ali Shah, he is from Islamabad, Pakistan, and he is covering Dengue Virus: Genomic Insights, Pathogenic Mechanisms, and Therapeutic Approaches for video: https://youtu.be/whrkkKR-NSY #denguevirus #virology #virologist #genomics #covid19 #virus #pathogen #pathology #immunology

1. THE DENGUE VIRUS : GENOMIC INSIGHTS, PATHOGENIC MECHANISMS, AND
THERAPEUTIC APPROACHES
PRESENTED BY
SAJID ALI SHAH
Department of Biotechnology, Quaid-I-Azam University, Islamabad

2. INTRODUCTION TO DENGUE
The dengue fever is (an arboviral disease), caused by dengue virus
It belongs to Flaviviridae family and the genus Flavivirus.
Aedes aegypti and Aedes albopictus.
DENV-1, DENV-2, DENV-3, DENV-4, and DENV-5
Infection caused by one serotype doesn’t produce immunity against the other serotypes
Swahili term "ki-dinga pepo". evil spirit derived Spanish word "dengue," which means "fastidious" or "careful"
United States used "break-bone fever" in an article in 1789, "bilious remitting fever" dandy fever," members around 1800.
The term "dengue" is used in English literature in 1828.

3. Dengue Virus
Infection
Dengue Fever
Dengue
hemorrhagic fever
Three phases
Febrile
Critical
convalescent
Undifferentiated
fever
Older children or adults
High fever
Retro-orbital pain
Myalgia
Arthralgia
Rash
Nonspecific
Febrile illness
Symptomatic
Asymptomatic
Dengue Shock
syndrome
Most severe form

4. EPIDEMIOLOGY
From 0.5 Million cases in 2000 to 4.2 million cases in 2019, The cases of dengue
has significantly increased by almost 8 times in the last 20 years.
During the COVID-19 pandemic an increase occurs in the incidence of Dengue.
 In Pakistan, more than 22,000 dengue fever cases were reported in 2017, followed
by 3200 cases in 2018, 24,547 in 2019, 3,442 in 2020, and 48,000 in 2021.
From 1st January to 27th September 2022, a total of 25,932 confirmed dengue
cases with 62 deaths were reported in Pakistan
Until now 157485 cases and about 1153 patients have been died due to dengue virus

5. STRUCTURE OF DENGUE VIRUS
DENV is an enclosed, tiny spherical virus with a positive
sense single-stranded RNA genome. DENV serotypes
(DENV1, DENV2, DENV3, and DENV4) share 70-80%
amino acid sequence similarity.
Dengue virus (DENV) shares genomic and structural
characteristics with other Flaviviruses which includes
Japanese encephalitis virus (JEV), yellow fever virus (YFV),
tick-borne encephalitis virus (TBEV) and West Nile virus
(WNV).
Membrane
Matrix protein
Capsid
Genome
Integrase
Reverse transcriptase
Protease
Surface membrane protein
Transmembrane envelope protei

6. GENOMIC ORGANIZATION

7. DENV PROTEINS AND FUNCTIONS
Structural proteins
• capsid protein (C) 114 amino acid
• Envelope protein ( E ) 495 amino acid
• Membrane protein 166 amino acids
Non-structural proteins
• NS1 352 amino Acid
• NS2a 218 amino acid
• NS2b 130 amino acid
• NS3 619 amino acids
• NS4a 127 amino acids
• NS4b 249 amino acids
• NS5 899 amino acid

8. Protein functions of structural and non-structural
genes in the dengue virus genome
Gene name Functions
Pre-membrane
(prM)
Target of antibody response, infection enhancement, viral entry, Viral assembly, and stabilization of proper
folding of the E protein.
Capsid (C) RNA encapsidation, Viral genome packaging and release, viral growth, and replication.
Envelope (E) Cell attachment, fusion, Antigenicity, immunological epitopes, and infectivity
NS1 RNA replication
NS2a antagonizing the host immune response, virion assembly, synthesis of viral RNA, inhibition of interferon
signaling, formation of virion and maturation.
NS2b RNA triphosphatase, Helicase and protease.
NS3 Polyprotein processing and unwinding and replication of RNA.
NS4a Interferon signaling inhibition.
NS4b Interferon signaling inhibition and Viral replication.
NS5 Nuclear localization, RNA polymerase, RNA capping, initiation of de novo RNA synthesis, methyl transferase
activity, role in innate immunity, and induction of interleukin 8.
3`UTR RNA synthesis, Replication, and host specific factors

9.  DENV CELL ENTRY RECEPTORS
LIFE CYCLE OF DENGUE VIRUS
(Kato, F., & Hishiki, T. (2016))

10. LIFECYCLE OF DENGUE VIRUS

11. PATHOGENESIS
Complex interaction between the host gene, virus, and host immune response.
Host variables such as anti-DENV NS1 antibodies, memory cross-reactive T cells,
autoimmunity, Antibody-Dependent Enhancement (ADE), and genetic diversity are important
contributors to disease susceptibility.
HLA-A*33 and HLA-A*0203 alleles, protective phenotype
 HLA-A*24 and HLA-A*0207 are harmful genetic variations

12. TRANSMISSION
• Aedes albopictus and Aedes Aegypti.
• Blood transfusions from infected
donors.
• Organ Transplant
• Maternal transmission.
Urban cycle
Jungle cycle
(Islam, M.T., et al, 2021)

14. DIAGNOSIS OR DETECTION
• Blood Parameters test.
• Platelets count, Hb%
• IgM- IgG ELISA
• Neutralization assays
• Nucleic acid amplification test
• Polymerase Chain Reaction (PCR)
• Bio sensors
• Microarray

15. PREVENTION
• Mosquito Control
• Insecticides
• Laboratory-engineered mosquitoes
• Clothes
• Mosquito netting
• Applying insect repellent.

16. TREATMENT
Bed Rest
Body fluid maintenance
Euphorbia hirta and Carica papaya, Quercus lusitanica,
Neem leaf extracts and Methanolic extracts of Plants (Andrographis paniculata,, Ocimum sanctum ,
Cymbopogon citratus, Pelargonium citrosum and Momordica charantia).
Corticosteroids
Antiviral drugs Protease inhibitors, ST-148 and nucleoside inhibitors. benzoxazole inhibitor ST-610 (RNA) ,
Iminosugars
Acetaminophen
Do not take aspirin or ibuprofen
Calcium along with vitamin D supplements can be used in DENV infection.

17. VACCINE
Dengvaxia (CYD-TDV) which is a live-attenuated, tetravalent, yellow-fever vaccine used in Mexico,
Thailand, Brazil, El Salvador, and Costa Rica,
Currently Phase 2 studies are being conducted for a new vaccine, Takeda's Tetravalent Dengue Vaccine
(TDV)
Two dengue vaccines, TV003/TV005, and DENVax are now being tested for effectiveness in Latin America
and Asia

18. Thank you