GROUP 19 Microbiology ,virology presentation

Microbiology 3

1. GROUP 19 Orthomyxoviridae: Influenza viruses

2. GROUP MEMBERS NAME REGISTRATION NUMBER ATEKANIZA DOREEN VU-BPC-2307-0886-DAY ASEPO PEACE ANGELLA VU-BPC-2301-0126-DAY ANGENGEUN EUNICE BLESSING VU-BPC-2307-0861-DAY AKORA BABRA E. VU-BPC-2209-1412-DAY AKIDING SHALOM ELSIE VU-BPC-2209-1157-DAY

3. Introduction Orthomyxoviridae comes from a Greek word, orthos meaning straight and myxa meaning mucus. It is a family of RNA viruses. It includes seven genera: Influenzavirus A, Influenzavirus B, Influenzavirus C, Influenzavirus D, Isavirus, Thogotovirus, and Quaranjavirus. The first four genera contain viruses that cause influenza in vertebrates, including birds, humans, and other mammals.

4. Types of Influenza viruses Influenza viruses A, B, and C are pathogenic in humans. Influenza type A (Alpha Influenza Virus): This type includes influenza A viruses of human and also widespread in animals, particularly aquatic birds, chicken, ducks, pigs, horses, and seals. Influenza type A is responsible for pandemic and for most cases of epidemic influenza (antigenically highly variable).

5. Influenza type B (Beta Influenza Virus): This type includes influenza B viruses which are mainly found in humans. Influenza type B may exhibit antigenic changes and sometimes causes epidemics. Influenza type C (Gamma Influenza Virus): This type includes influenza C viruses of human and swine. Influenza type C is antigenically stable. Influenza type D (Delta Influenza Virus): This type includes influenza D viruses which are mainly found in pigs and cattle.

6. What are the key structural components of the Orthomyxoviridae family, specifically the Influenza virus, and how do they contribute to viral replication and antigenic variation (antigenic drift and shift)?

7. S tructural components of the Orthomyxoviridae family

8. The influenza virus virion is pleomorphic(ability to alter their morphology, biological functions or reproductive modes in response to environmental conditions). The viral envelope can occur in spherical and filamentous forms. The viral envelope is composed of a lipid bilayer membrane in which the glycoprotein spikes are anchored and encloses the nucleocapsids The ribonuclear proteins are filamentous and fall in range of 50 130nm long and 9-15nm in diameter with helical symmetry.

9. Viruses of the family Orthomyxoviridae contain six to eight segments of linear negative-sense single stranded RNA. This segmentation allows for reassortment, where by genetic material from different viral strains is mixed during co-infection of a host cell causing an emergence of new viral strains with different gene combinations. The best characterized of the influenza virus proteins are hemagglutinin and neuraminidase , two large glycoproteins found on the viral envelope Hemagglutinin is a lectin that mediates binding of the virus to target cells and entry of the viral genome into the target cell. Neuraminidase is an enzyme involved in the release of progeny virus from infected cells by cleaving sugars that bind the mature viral particles.

10. Hemagglutinin and neuraminidase are targets of the host immune response and changes in their structure can cause antigenic shift and drift. Matrix protein(M1);is located beneath the viral envelope and is important in viral assembly and budding.it interacts with viral RNA segments and the envelope proteins facilitating formation of new virus particles. Nucleoprotein(NP); it binds to viral RNA segments forming a complex which protects genetic material from degradation helping in viral replication and transcription. Envelope proteins; the viral envelope is composed of a lipid bilayer having glycoproteins including HA,NA, and M2. M2 is a transmembrane protein regulating the pH of the viral interior which is important during viral uncoating and replication.

11. Replication cycle of the virus

12. Influenza is transmitted from infected mammals through the air by coughs or sneezes, creating aerosols containing the virus and from infected birds through their droppings. It can also be transmitted by saliva, nasal secretions , feces and blood once in contact. The viruses bind to a cell through interactions between its hemagglutinin glycoprotein and sialic acid sugars on the surfaces of epithelial cells in the lung and throat. The cell imports the virus by endocytosis.

13. In the acidic endosome, part of the hemagglutinin protein fuses the viral envelope with the vacuole's membrane , releasing the viral RNA(vRNA) molecules, accessory proteins and RNA –dependent RNA polymerase into the cytoplasm. These proteins and vRNA form a complex that is transported into the cell nucleus where the RNA-dependent polymerase begins transcribing complementary positive sense cRNA. The cRNA is either exported into the cytoplasm or remains in the nucleus. Newly synthesized viral proteins are either secreted through the Golgi apparatus onto the cell surface or transported back into the nucleus to bind vRNA and form new viral genome particle.

14. Negative sense vRNA that forms the genomes of future viruses, RNA dependent RNA transcriptase and other viral proteins are assembled into a virion. hemagglutinin and neuraminidase molecule cluster into bulge in the cell membrane. the vRNA and viral core proteins leave the nucleus and enter this membrane protrusion. The mature virus buds off from the cell in a sphere of host phospholipid membrane, acquiring hemagglutinin and neuraminidase with its membrane coat. Viruses adhere to the cell through hemagglutinin , the mature viruses detach once their neuraminidase has cleaved, sialic acid residues from the host cell. After the release of new influenza virus, the host cell dies.

15. Orthomyxoviridae viruses replicate in the nucleus because their machinery can not make their own mRNAs. They use cellular RNAs as primers for initiating the viral mRNA synthesis in a process called cap snatching. Once in the nucleus the RNA polymerase protein PB2 finds a cellular pre-mRNA and binds to its 5’ capped end. Then RNA polymerase PA cleaves off the cellular mRNA near the 5’ end and uses this capped fragment as a primer for transcribing the rest of the viral RNA genome in the viral mRNA.

16. Since RNA proof reading enzymes are absent, the RNA –dependent RNA transcriptase makes a single nucleotide insertion roughly every 10 thousand nucleotides , which is the approximate length of the vRNA. Nearly every newly manufactured influenza virus will contain a mutation in its genome. the separation of the genome into eight separate segments of vRNA allows mixing of the genes if more than one variety of influenza virus has infected the same cell. The resulting alteration in the genome segments packaged into viral progeny confers new behaviors , like the ability to infect new host species, over coming protective immunity of host populations to its old genome.

17. The segmented genome,M1 protein, nucleoprotein and envelope proteins work together to facilitate viral replication. The segmented genome allows for reassortment, M1proteins,nucleoprotein and envelope proteins allow for viral assembly, budding and uncoating. Antigenic drift being a gradual process of genetic change in the hemagglutinin and neuraminidase genes leads to changes in the structure of these proteins reducing the effectiveness of the hosts immune response allowing the virus to evade the hosts immune system and spread. Antigenic shift occurs when two or more influenza virus strain co infect a host cell and reassort their genetic material resulting in the emergence of new viral strains with many different combination of neuraminidase and hemagglutinin genes differing from the circulating strains which may be fatal to the host.

18. Discuss the global burden of influenza pandemics. How does the ability of Influenza viruses to mutate and reassort genes complicate vaccination efforts?

19. Historical Influenza Pandemics 1918 Spanish Flu was the deadliest influenza pandemic in recorded history, causing an estimated 50–100 million deaths worldwide. 1957 Asian Flu pandemic originated in East Asia and led to about 1–2 million deaths globally. 1968 Hong Kong Flu caused an estimated 1 million deaths, this pandemic spread worldwide and continues to circulate today in a slightly mutated form. 2009 Swine Flu caused relatively fewer deaths around 150,000–575,000, but it primarily affected younger populations.

20. The virus exhibits antigenic drift, where its surface proteins gradually change, rendering existing vaccines less effective. Additionally, antigenic shift occurs when different subtypes combine, creating new strains to which the population has little immunity. This rapid evolution makes it challenging to develop effective vaccines, as the virus can mutate before a vaccine can be produced and distributed. Furthermore, the need for frequent updates to account for new strains adds complexity to vaccination efforts, making it essential to stay informed about the virus' evolving characteristics.

21. Antigenic Drift (Gradual Mutation) Antigenic drift refers to the slow, continuous accumulation of point mutations in the genes encoding surface proteins hemagglutinin (HA) and neuraminidase (NA). These mutations occur because the influenza virus uses an RNA-dependent RNA polymerase for replication, which lacks proofreading ability, resulting in frequent errors. These small changes in viral antigens help the virus evade the host immune system, meaning immunity from previous infections or vaccinations may become less effective over time. This necessitates the annual update of flu vaccines to match the most current circulating strains.

22. Antigenic Shift (Gene Reassortment) Antigenic shift occurs when two different strains of influenza viruses from different species e.g., human, avian, or swine influenza strains infect the same host cell and exchange gene segments. The reassortment of gene segments can result in the emergence of a completely novel influenza strain. This process is responsible for the sudden emergence of new influenza subtypes, which can lead to pandemics because the human population has little to no pre-existing immunity to the new strain.

23. Challenges in Vaccination Efforts The continuous small mutations in the HA and NA genes mean that the virus is constantly evolving making previously effective vaccines less protective as the viral strains circulating in the population change year to year. As a result, the influenza vaccine has to be reformulated each season to target the most recent strains.

24. While vaccines for many viral diseases provide long-term immunity, the constant evolution of influenza through antigenic drift makes the production of a universal influenza vaccine challenging. Once a novel pandemic strain emerges, public health agencies must quickly develop a new vaccine specific to that strain which can take several months, during which time the virus can spread globally, leading to high levels of illness and death before vaccines become available.

25. Examine the clinical presentation and complications of seasonal influenza infections. What groups are at higher risk for severe influenza, and how are they managed?

26. Clinical Presentation Fever Cough Sore throat Myalgia (muscle aches) Chills and Fatigue Headache Nasal congestion R hinitis Malaise Runny nose

27. Complications Multi-organ failure or death. Pneumonia Acute bronchitis Croup Acute otitis media Cardiac issues (e.g. myocarditis or pericarditis) Asthma flare-up Acute respiratory distress syndrome Encephalitis and/or encephalopathy Reye syndrome

28. Management Vaccination Early antiviral treatment Antihistamines Decongestants Expectorants Cough suppressants Hospitalization to monitor for complications Nutritional Support

29. What are the current antiviral therapies and vaccines available for influenza, and how effective are they in preventing and treating infection?

30. Antiviral drugs include; Neuraminidase Inhibitors Oseltamivir Zanamivir Peramivir Neuraminidase inhibitors block the viral neuraminidase enzyme, preventing the release of new viral particles from infected cells and limiting the virus’s ability to spread in the body.

31. Cap-dependent Endonuclease Inhibitor Baloxavir Marboxil This class of antivirals interferes with viral mRNA synthesis by inhibiting the virus's ability to cap-snatch host RNA, thus preventing viral replication. Antiviral drugs are effective in reducing illness duration by 1-2 days, lowering the risk of complications such as pneumonia, and reducing the need for hospitalization in high-risk individuals.

32. Vaccines include; Inactivated Influenza Vaccines High-dose, egg-based influenza vaccine Standard-dose, adjuvanted egg-based influenza vaccine Adjuvanted Inactivated Influenza Vaccine Fluad Live Attenuated Influenza Vaccine Unadjuvanted Nasal spray Recombinant Influenza Vaccine Flublok

33. The effectiveness of influenza vaccines depends on how well the vaccine strains match the circulating virus strains in a given season. On average, vaccine effectiveness ranges from 40-60% but can be lower if the circulating strains undergo significant antigenic drift after the vaccine strains are selected.

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