1. Influenza: Pathogenesis Overview ● Entry Route ● Infection Cycle ● Virulence ● Clinical Course ● Complications ● Factors

2. Influenza: Pathogenesis Entry Route Influenza is often classified as a respiratory disease, entering through the respiratory tract. The virus is passed from person to person via aerosolized droplets exhaled from the infected host. The new host inhales the aerosol and the viruses are deposited along the respiratory tract.

3. Influenza: Pathogenesis Infection Cycle The infection sites are the epithelial cells of the upper and lower respiratory tract. Where the virus will bind to host cells, replicate and spread.

4. Influenza: Pathogenesis Infection Cycle Replication And Spread of Virus: Once bound, the virus enters the cell where it takes advantage of the host cell machinery to making copies of its RNA within hours. New virus particles are released, "budding", from the infected cell and infect more cells within the respiratory tract.

5. Influenza: Pathogenesis Infection Cycle Host Response Early Response - The host responds locally to the fast growing, fast spreading infection with respiratory symptoms. Cytokines (proteins that signal other cells to react) are released from the infected cells. These indirectly cause the body temperature to increase. Some mechanism of systemic response are not fully understood. Later Response - adaptive immune response may take days as the immune system learns to recognize the virus. And then marshalling B Cells and T lymphocytes to clear the virus.

6. Influenza: Pathogenesis Virulence Influenza A - the most virulent. Antigenic variation allows for extensive replication and spread while avoiding the immune system. Influenza B - less virulent and less antigenic variation. Influenza C - this is the least virulent of the influenza virus and may have minor cold-like symptoms.

7. Influenza: Pathogenesis Virulence Factors  A study in mice showed that the influenza pandemic of 1918 caused a hyperactive inflammatory response leading to respiratory failure.  Researchers have discovered that a small change in one of the ten genes, the PB2 gene, in the H5N1 avian influenza virus codes an enzyme that forces the host cell to make more viruses.  Antigenic variation in the Ha And Na surface glycoproteins allows the virus to evade immune response an important factor in virulence

8. Influenza: Pathogenesis Virulence Factors Neuramidase Helps release new Viruses

9. Influenza: Pathogenesis Clinical Course Typically, symptoms appear within a few days of exposure: the incubation period. Starting with rapid onset of fever, chills, general malaise, headache, cough and sore throat. The acute symptoms last 3-4 days, sometimes lasting up to 8 days. Then dimishing thereafter, through the end of the second week. The cough and general discomfort may last longer.

10. Influenza: Pathogenesis Complications Most commonly, complications involve the respiratory system. These often include: Secondary bacterial pneumonia Primary viral pneumonia Mixed viral and bacterial pneumonia Exacerbation of existing pulmonary disease Croup (in children) Other complications are rare: cardiac involvement, myositis and toxic shock syndrome.

11. Influenza: Pathogenesis Infection Factors Host Factors Host factors affect the hosts susceptibility to infectionImmunocompetence: Immune diseases (such as HIV/AIDS), immunosupressive therapy (cancer chemotherapy) Specific Immunity: vaccination, prior infection Host target receptor cells: Available and Accessible Enzymes: available for viral reproduction

12. Influenza: Pathogenesis Infection Factors Viral Factors Viral factors effect the success of the virus to infect its host. Evasion of the immune response: Antigenic shift and recombinant techniques Bind to host cells: a first step in the infection. Replication Evironment:Ability to reproduce in the host and shed (spread) their progeny Modulation of pathological effects: keep the host alive long enough to spread beyond the host.

13. Influenza: Pathogenesis Sources and Resources  Bernd Sebastian KampsChristian HoffmannWolfgang Preiser, Influenza Report: 2006: http://www.influenzareport.comhttp://www.influenzareport.com  Maria Zambon, Epidemiology and Pathogensesis of Influenza, Jrnl of Antimicrobial Chemotherapy, No 44, 1999  A Small Genetic Change makes Flu Virus Deadly, NIH News, 6 Sept, 2001: http://www3.niaid.nih.gov/news/newsreleases/2001/genchange.htm http://www3.niaid.nih.gov/news/newsreleases/2001/genchange.htm  Jason White Medical Ecology:: Influenza, 2004 http://www.medicalecology.org/diseases/influenza/influenza.htm