Introduction to Crimean Hemorrhagic Fever Virus.pptx

Introduction to Crimean Hemorrhagic Fever Virus or Congo Virus

1. Crimean Congo Hemorrhagic fever virus

2. CONTENT INTRODUCTION LIFE CYCLE MODE OF TRANSMISSION DISEASE IN HUMANS PRVVENTIVE MEASURES 2

3. INTRODUCTION: 3 Crimean Congo hemorrhagic fever virus (CCHFV) is a tick borne Nairovirus within the family Bunyaviridae which causes severe hemorrhagic fever with a mortality of 30% in more than 30 countries worldwide. Public health problem in many regions of the world-e.g., Asia, Eastern Europe, Africa, and Russia.

4. History: 4 First described in the Crimea, Russia in 1944 during an outbreak which involved 200 cases in soviet military personnel. Later in 1956 it was found that the causative agent was identical to a virus isolated from a patient in Congo and the name Crimean Congo hemorrhagic fever virus was adopted after that.

5. 5 Crimean Congo hemorrhagic fever virus is a member of Nairovirus genus of the family Bunyaviridae . Classification Of (CCHF) virus: Phylum: Negarnaviricota Class: Ellioviricetes Order: Bunyavirales Family: Nairoviridae Genus: Orthonairovirus There are 7 recognized species in the genus Nairovirus containing 34 viral strains.

6. Structure of the virion: 6 Capsid: Helical symmetry The virion is spherical, 100 nm in diameter. Contains three structural proteins (2 glycoproteins Gn ,Gc & a nucleocapsid protein NP+L protein). Host cell derived bilipid layer envelope (5-7 nm thick) through which virus coded glycoprotein spikes protrude out.

7. 7 Genome: Trisegmented, negative sense, single-stranded RNA genome (~ 19.1 kb). Segments : small(1.6kb), medium(5.4kb), large(12.1kb) which encode nucleocapsid protein, glycoprotein precursors & RNA dependent RNA polymerase respectively. The genome is encapsidated by the NP and RNA polymerase which form genomic ribonucleoprotein complex. Complementary non coding regions (NCRs) are present at the 3`and 5` termini of the all there segments of CCHFV which are non covalently linked and contribute to the circular appearance of the genome the nine terminal nucleotides (5`- UCUCAAAGA and 3`-AGAGUUUCU) are conserved between Nairovirus and serve as viral promoter regions. The NCRs are necessary for the viral (RdRp or L protein) to bind and initiate transcription and/or replication of the viral genome.

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9. Replication of virion: 9 Attachment : It is initiated by the binding of envelope glycoproteins (Gn and Gc) to cell surface–associated receptors. The host receptor of CCHFV has not been identified, although a recent study has suggested that cell surface nucleolin plays a necessary role in virus entry and Gc is essential for binding to the cell.

10. 10 Entry: CCHFV entry is mediated by clathrin-dependent endocytosis, which is pH dependent. The virus is endocytosed in coated vesicle which subsequently becomes acidified. the acidification triggers a fusion of viral membranes and endosomal membranes and results in the release of viral nucleocapsid into cell cytoplasm.

11. 11 Transcription: Transcription entirely occurs in cytoplasm. After uncoating of viral genome, primary transcription of negative sense vRNA to complementary mRNA occurs through interaction of the virion –associated polymerase (L protein) and the three viral RNA templates. Cap snatching; The L protein is believed to function first as an endonuclease to cleave capped oligonucleotide from host mRNA to serve as transcription primers.

12. 12 Translation: S-segment gene product: After translation of the mRNA of S segment Nucleoproteins (NP) are formed. The N proteins are of size ~48-54 kd. M- Segment gene products: After translation of the mRNA of M segment glycoprotein precursors(GPC) are formed which later mature to form Gn and Gc. The Gn is of size~108-120kd and Gc is of size ~29-41kd. L-segment gene products: After translation of mRNA of L-segment L-protein which is a multifunctional enzyme RNA dependent RNA polymerase is formed which is of size ~240-260kd.

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14. 14 Replication:   Since CCHFV is a negative strand RNA virus, genomic RNPs are used as template to synthesize capped mRNA and produce antigenomic RNPs. During the replication of the genomic RNPs, a cRNA is synthesized by the L protein and NP subunits are added to the elongating strands to obtain antigenomic RNPs, and in turn the cRNA of the antigenomic RNPs is used a template to obtain genomic RNPs. The encapsidated forms of the cRNA and vRNA are respectively defined as antigenomic and genomic RNPs

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16. 16 Assembly, Packaging and Release: Assembly: Viruses in families such as rhabdoviridae, orthomyxoviridae and paramyxoviridae utilize M protein for nucleocapsid and viral envelope proteins interaction for assembly.In contrast crimean Congo hemorrhagic fever virus rely on direct interaction for triggering the virion assembly. Packaging GPC (glycoprotein precursor) undergoes maturation and processing in Golgi Complex results in the formation of Gn and Gc. RNPs and NP are localised in the perinuclear region.

17. VIRION RELEASE: Nucleocapsid complexes bud into the Golgi membrane with Gn and Gc embedded Virion particle is formed inside Golgi apparatus Virions are transported to cell membrane by vesicles and released by exocytosis Gn and Gm embedded into cell membrane through Golgi vesicles Virion bud from cell membrane, not through Golgi apparatus. 17 Two mechanisms

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19. Host range and risk population: 19 Host range: The hosts of the CCHFV include a wide range of wild and domestic animals such as cattle, sheep and goats Many birds are resistant to infection, but ostriches are susceptible The main cellular targets of infection are mononuclear phagocytes, endothelial cells and hepatocytes. Risk population: Animal herders, livestock workers, and slaughter houses in endemic areas are at risk Healthcare workers in endemic areas are at risk of infection through unprotected contact with infectious blood and body fluids.

20. 20 Vectors: Animals become infected from the bite of infected ticks. A number of tick genera are vectors of CCHF (most commonly Hyalomma genus).

21. Mode of transmission: 21 Mode of transmission: Humans can be infected by direct contact with blood or other infected tissues from livestock having viraemia, or a tick bite. CCHFV can be transmitted from one infected human to another by contact with infectious blood or body fluids. Documented spread of CCHF has also occurred in hospitals due to improper sterilization of medical equipment reuse of injection needles, and contamination of medical supplies.

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23. 23 Clinical features among humans: Infection is acute Incubation period of illness depend on the mode of acquisition of Virus With a tick bite incubation period is only 2-3 days, maximum of 9 days. Contact with infected blood, tissues the incubation period is 5-6 days, max 13 days. Common symptoms of Crimean-Congo hemorrhage virus fever (CCHF) are; Headache vomiting Back pain High fever Myalgia (pain in muscles) Malaise photophobia

24. 24 Diagnosis : There are no rapid diagnostic tests. IgG and IgM antibodies may be detected in serum by enzyme-linked immunoassay (the "ELISA" or "EIA" methods) from about day six of illness. IgM remains detectable for up to four months, and IgG levels decline but remain detectable for up to five years. Treatment: The antiviral drug RIBAVIRIN is used. Both oral and intravenous formulations seem to be effective.

25. 25 Prevention and control: It is difficult to prevent or control CCHFV infection in animals and ticks as the tick-animal-tick cycle usually goes unnoticed and the infection in domestic animals is usually not apparent. So tick control with ACARICIDES is only a realistic option. Vaccines: There are no vaccines available for use in animals. Although an inactivated, mouse brain derived vaccine against CCHFV has been developed and used on small scale in eastern Europe, there is currently no safe and effective vaccine widely available for human use.

26. 26 Other negative sense segmented RNA viruses’ families:

27. 27 References: https://en.wikipedia.org/wiki/Crimean– Congo_hemorrhagic_fever https://en.wikipedia.org/wiki/Crimean– Congo_hemorrhagic_fever https://en.wikipedia.org/wiki/Crimean– Congo_hemorrhagic_fever https://www.cdc.gov/vhf/crimean-congo/index.html https://www.mdpi.com/1999-4915/8/4/106 https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004390

28. 28 THANK YOU