1. 1 Coronaviruses (C57, p. 565)

2. 2 @ Coronaviruses are named for the solar corona-like appearance (the surface projections) 2-2

3. 3 Coronaviruses are the second most prevalent cause of the common cold (Rhinoviruses are the first). In 2002, severe acute respiratory syndrome (SARS) was induced by SARS- CoV with 8000 infected individuals and at least 784 deaths.

4. 4 2-4 Structure: + single-strand RNA virus with envelope Replication

5. 5 Diseases caused by Coronaviruses Virus infects epithelial cells of upper respiratory tract. The optimal temperature for viral growth is 33 to 35 ℃, so infection is restricted in upper respiratory tract. Virus is spread by aerosols or droplets of sneezes or cough. Infection causes 10 to 15 % of upper respiratory tract infections (common cold) and pneumonia.

6. SARS-CoV is spread by respiratory route to causes SARS within 10-day exposure. SARS is a form of atypical pneumonia characterized by high fever (> 38°C), chills, rigors ( 發燒前的寒戰 ), headache, dizziness, malasis, myalgia, cough or breathing difficulty. About 20% cases develop diarrhea, and mortality is about 10%. @ Medical personnel are most vulnerable. (Medical personnel can reduce risk with correct knowledge, attitude, and responsibility.)

7. For SARS 1.Is virus spread by the sweat, urine, and feces of patients or wild animals? 2.Infection is detected by RT-PCR, serology, and EM. Virus isolation must be performed in BSL 3 condition. 5. Quarantine of patients and screening for fever travelers from outbreak regions to limit SARS infection. 6. No specific antiviral therapy is available.

8. 8 1.Control of common cold caused by the virus is difficult and unnecessary because the infection is mild. 2.No vaccine or specific antiviral therapy is available.

9. 9 In p. 568 Coronaviruses Common cold: A 25-year-old person develops runny nose, mild cough, and malaise with a low-grade fever. A co- worker in the office has had similar symptoms for the past few days. SARS: A 45-year-old businessman returned from a 2-week trip to China. Five days after returning home to the United States, he developed a fever of 101.5°F (38.6°C) and cough. Now he observes that it is harder to catch his breath. (Do not worry about misdiagnosis of SARS because you will know when it comes.)

10. 10 Noroviruses ( 諾沃克病毒, 杯狀病毒 )

11. 11 Noroviruses ( Small, round gastroenteritis viruses ) Include Astroviruses Caliciviruses Norwalk-like viruses (Norwalk virus) Virus is with + sense RNA genome and capsid, but no envelope.

12. 12 1.Viral infections cause diarrhea with nausea and vomiting (abdominal cramps) in children, and diarrhea in adults. Disease develops 48 hours after incubation and resolves after 48 hours without problems 2.No specific treatment.

13. 13 -- Virus is transmitted by fecal-oral route and accounts for 50% of gastroenteritis outbreak (23,000,000 cases in US per year). -- About 70% children have antibodies to the virus by age 7 years. --Outbreaks may be minimized by handling food and water carefully.

14. 14 Rhabdoviruses (C60, p. 593)

15. 15 GM NS + L = RNA dependent RNA polymerase Rhabdovirus (C60, p. 593) rabies virus (a human pathogen) 1. Structure (bullet-shape) -ssRNA (12 kb), non-segmented capsid envelope

16. 16 40 - RNA + RNA 2. Replication

17. 17 3. Pathogenesis and immunity : Infection causes about 100% fatality Incubation period, ranging from 1 week to years with an average of 1-2 months, depends on 5 factors (p. 595). Ab is protective but appears late. Via nicotinic acetylcholine receptors

18. 18 4. Epidemiology of rabies -- It is a classical zoonotic infection carried by domestic animals and wild animals (Fig. 3, p. 595). There was 8,000 animal cases in US (next slide). -- It is found worldwide except Australia. -- It causes 40,000 to 70,000 death worldwide with 25,000 cases in India annually. --One case per year in US because of effective dog vaccination.

19. 19

20. 20 Box 60-4. Clinical Summaries Rabies: A 3-year-old girl was found to have a bat flying in her bedroom. The bat apparently was there all night. There was no evidence of any bite wound or contact, and the bat was caught and released. Three weeks later the child developed a change in behavior, in which she was irritable and agitated. She quickly became confused and uncontrollable, thrashing about and unable to handle her secretions. She eventually became comatose and died from respiratory arrest. Most rabies are transmitted by animal bites and some are transmitted by the inhalation of aerosolized virus. Practice the case study in p. 599.

21. 21 Disease PhaseSymptoms Time (days)Viral Status Immunologic Status Incubation phase Asymptomatic60-365 after bite Low titer, virus in muscle - Prodrome phase Fever, nausea, vomiting, loss of appetite, headache, lethargy, pain at site of bite 2-10Low titer, virus in CNS and brain - Neurologic phase Hydrophobia, pharyngeal spasms, hyperactivity, anxiety, depression 2-7High titer, virus in brain and other sites Detectable antibody in serum and CNS CNS symptoms: loss of coordination, paralysis, confusion, delirium ComaComa: cardiac arrest, hypotension, hypoventilation, secondary infections 0-14High titer, virus in brain and other sites - Death----

22. 22 6. Diagnosis: a + b a. The occurrence of neurological symptoms in a person bitten by an animal. b. Laboratory confirmation: Negri bodies in neurons of 70 to 90% patients. virus antigens in tissues RT-PCR virus isolation serology Negri bodies in human brains

23. 23 7. Treatment and prophylaxis: A.Post-exposure prophylaxis initiates in persons exposed by bite or contamination, including -- local treatment of the wound (clean and inactivate the virus and administration the antirabies serum around the wound) -- one shot of human rabies immunoglobulin (HRIG) -- 5 shots of killed-virus vaccine on day 0, 3, 7, 14 and 28 by intramuscular injection (or day 0, 3, 7, 28 and 90 by intramuscular injection) ( Louis Pasteur developed the first generation of killed-rabies vaccine.) B. Pre-exposure prophylaxis includes 3 shots of vaccine providing 2-year protection. Live attenuated viruses are used for immunizing animals.

24. 24 Filoviruses ( 絲狀病毒 )

25. 25 Filoviruses 1. Structure: filamentous - ssRNA capsid envelope

26. 26 2. Virus replicates in cytoplasm in a manner similar to rhabdoviruses.

27. 27 3. African hemorrhagic fevers is caused by Marburg virus in Kenya or Ebola virus in Congo (Zaire). 4. Marburg virus infection was first detected in laboratory working exposed to monkey tissues. Rare cases have been seen. Ebola outbreak is sporadic. Virus specific Ab is found in 18% population in rural areas of central African. Virus can be spread from monkeys to humans and between humans. 5. These 2 viruses are the most sever causes of viral hemorrhagic fevers. The illness may usually begins with flu like symptoms (headache and myalgia)  nausea, vomiting, and diarrhea  rash  hemorrhage in multiple site especially GI tract. Death may occur in 90% cases.

28. 28 6. Lab. diagnosis -- Specimens must be handled in BSL 4 lab. -- Detection of viral antigen and Ab and RT-PCR to confirm infection 7. Interferon and Ab-containing serum are tested for treatment. Quarantine stops transmission.

29. 29 Bornaviruses

30. 30

31. 31 Borna disease virus (Bornaviridae) 1. Structure -- negative single-strand RNA (8.9kb) virus with envelope 2. Virus replicates in the nucleus 3. It was first described in 1885 as "heated head disease" of cavalry horses in 1885 in the town Borna, GermanyBorna

32. 32 3. Neurotropic virus can spread to the central nervous system to cause fatal immuno-mediated meningoencephalitis to result in learning and memory loss in animals. 4. Infected animals suffer neuropsychiatric diseases, including depression, bipolar disorder, schizophrenia, and autism. (Virus causes or exacerbates disease.) 5. Patients with these diseases tend to have virus in blood cells or virus-specific Ab in sera. 6. Transmission of virus is unknown. (Can virus spread from horses to humans because high levels of human infection after horse outbreak?) 7. Infection can be detected by RT-PCR and serology. 8. Virus is sensitive to ribavirin.