بسم الله الرحمن الرحيم

1. بسم الله الرحمن الرحيم

2. Classification of DNA Viruses

3. 1-Herpesviruses

4. 1-Herpesviruses

5. 1-Herpesviruses Herpes viruses-1

6. Herpesviruses Varicella viruses

7. Herpesviruses Zosterviruses

8. Herpesviruses Epstein-Barr virus

9. Adenovirus • Upper & lower tract respiratory disease (pharyngitis & pneumonia). • Entericstrains cause diarrhea. • Transmitted by respiratory droplet , iatrogenic in eye disease & fecal–oral with enteric strains. • Live vaccine against types 3, 4, & 7 is used in military to prevent pneumonia

10. Papillomavirus Human Papillomavirus • Papillomas (warts); condylomata acuminata (genital warts); carcinoma of cervix & penis. • Transmitted by direct contact of skin&genital lesion • Two early viral genes, E6 & E7, encode proteins that inhibit activity of proteins encoded by tumor suppressor genes, p53 gene & retinoblastoma gene, respectively. • Vaccine containing capsid proteins of four HPV types (6, 11, 16 and 18) is available.

11. Papillomavirus Human Papillomavirus

12. Hepadnavirus Hepatitis B Virus • Hepatitis B & hepatocellular carcinoma. • Transmitted by blood, during birth & sexual intercourse. • Hepatocellular injury due to immune attack by cytotoxic (CD8) T cells. • Antigen–antibody complexes cause arthritis, rash, & glomerulonephritis. • 5% of HBV infections result in a chronic carrier. • Chronic hepatitis, cirrhosis & hepatocellular carcinoma can occur (integration of part of viral DNA intohepatocyte DNA).

13. Hepadnavirus Hepatitis B Virus • Laboratory Diagnosis • Three serologic tests are commonly used: • 1- Surface antigen (HBsAg) • 2- Surface antibody (HBsAb) • 3- Core antibody (HBcAb). • Detection of HbsAg ≥6 monthschronic carrier. • Presence of e antigeninfectious chronic carrier. • “Window" phase : HBV-infected person has neither detectable HBs antigen nor HBs antibody & diagnosed by detecting HB core antibody.

14. Hepadnavirus Hepatitis B Virus • Treatment • Alpha interferon & lamivudinereduce inflammation associated with chronic hepatitis B but does not cure carrier state. • Prevention • (1) vaccine that contains HBsAg as immunogen • (2)hyperimmune serum globulins obtained from donors with high titers of HBsAb

15. Classification of RNA Viruses

16. Classification of RNA Viruses

17. Picornavirus Enteroviruses: Poliovirus • Range of responses to poliovirus infection includes: • (1) inapparent, asymptomatic infection • (2) abortive poliomyelitis • (3) nonparalytic poliomyelitis • (4) paralytic poliomyelitis. • Transmission by fecal–oral route & humans are natural reservoir. • Virus replicates in pharynx & GI tract & spread to local lymph nodes & then through blood to CNS.

18. Picornavirus Enteroviruses: Poliovirus • Most infections are asymptomatic or very mild. • Aseptic meningitis is more than paralytic polio. • Paralysis is the result of death of motor neurons, anterior horn cells in the spinal cord. • Virus in spinal fluid indicates CNS infection . • Virus in stools indicates infection ( not necessarily disease) as it is found in GIT of asymptomatic carriers.

19. Picornavirus Enteroviruses: Poliovirus • Disease can be prevented by: • - Salk: inactivated vaccine • - Sabin: live, attenuated vaccine • both induce humoral antibody that neutralizes virus in bloodstream. • Sabin vaccine has been preferred vaccine as : • Oral vaccine • Induces intestinal IgA, that prevent GIT infection • Induces immunity of longer duration

20. Picornavirus Enteroviruses: Hepatitis A Virus • Hepatitis A. • Transmission by fecal–oral route. Blood-borne transmission is uncommon because viremia is brief & of low titer. • Virus replicates in GIT then spreads to liver during brief viremic period. • Virus is not cytopathicforhepatocyte& hepatocellular injuryis caused byimmune attack bycytotoxic T cells. • Vaccinecontains killed virus. Administration of immune globulin during incubation period

21. Picornavirus Enteroviruses:Coxsackie Viruses • It causes the following diseases: • -Aseptic meningitis, Myocarditis, pericarditis • -Herpangina(fever, sore throat & tender vesicles in oropharynx) • -Pleurodynia(fever & severe pleuritic-type chest pain due to an infection of the intercostal muscles not of pleura • - Hand, foot &mouth disease (vesicular rash on hands & feet & ulcerations in mouth, mainly in children). • -Coxsackie virus B4 may cause juvenile diabetes • Transmissionby fecal–oral route. • Initial site of infection is oropharynx, but main site is GI tract then spreads through blood to various organs.

22. Picornavirus Rhinoviruses • Common cold. • There are more than 100 serotypes,which explains why the common cold is so common. • They are destroyed by stomach acid • Transmission by aerosol droplets & • hand-to-nose contact • Infection is limited to mucosa of upper respiratory tract & conjunctiva. • Virus replicates best at low temperatures of nose & less well at 37°C.

23. Influenza Virus Orthomyxovirus • Influenza. Influenza A cause worldwide epidemics. • It has two major antigens ; hemagglutinin (HA) & neuraminidase (NA) on separate surface spikes. • Antigenic shift in these proteins as a result of reassortment of RNA segments accounts for the epidemics of influenza • Antigenic drift due to mutations • also contributes.

24. Orthomyxovirus Influenza Virus • Antigenicity of internal nucleocapsid protein determines virus is A, B or C influenza virus. • Transmission by respiratory droplets. • Infection limited to epithelium of respiratory tract. • Neuraminidase inhibitor, oseltamivir (Tamiflu, drug of choice) & Zanamiviris used in treatment.

25. Orthomyxovirus Influenza Virus Two types of vaccines are available: 1-killed (subunit) vaccine: purified HA & NA. 2- Live, temperature-sensitive mutant of influenza virus. The virus replicates in cool nasal passages & induces secretoryIgA, but not in warm lower respiratory tract.

26. Paramyxovirus Measles Virus • Measles& Subacute sclerosing panencephalitis. • Transmission by respiratory droplets. • Initial site of infection is upper respiratory tract & spreads to local lymph nodes then via blood to other organs & skin. • Maculopapular rash is due to cell-mediated immune attack by cytotoxic T cells on virus-infected vascular endothelial cells in the skin. • Vaccine contains live, attenuated virus, given in combination with mumps & rubella vaccines.

27. Paramyxovirus Mumps Virus • Mumps. Bilateral orchitis & sterility is rare • Transmission by respiratory droplets. • Initial site of infection is upper respiratory tract & spreads to local lymph nodes then via blood to other organs, especially the parotid glands, testes, ovaries, meninges & pancreas. • Vaccine contains live, attenuated virus, given in combination with measles and rubella vaccines

28. Paramyxovirus Respiratory Syncytial Virus • Bronchiolitis &pneumonia in infants & otitis media in older children. • Transmission by respiratory droplets. Paramyxovirus Parainfluenza Virus • Bronchiolitis in infants, croup in young children & common cold in adults. • Transmission by respiratory droplets.

29. Togavirus Rubella Virus • Rubella & Congenital rubella syndrome (congenital malformations, affecting cardiovascular & CNS) • Transmission by respiratory droplets & across the placenta from mother to fetus (during first trimester) • Initial site of infection is nasopharynx, then to local lymph nodes & disseminates to skin via blood. Rash due to viral replication & immune injury. • Vaccine contains live, attenuated virus, given in combination with measles and mumps vaccine.

30. Coronavirus Coronavirus • Common cold & SARS (severe acute respiratory syndrome). • Transmission by respiratory droplets. • It Infects mucosal cells of respiratorytract.

31. Rhabdovirus Rabies Virus • Rabies (encephalitis) • Transmission by animal bite & aerosols of bat saliva. • Viral receptor is the acetylcholine receptor. • Replication of virus at site of bite, followed by axonal transport up nerve to CNS then replicating in brain & migrates to salivary glands & saliva. • Tissue stained with fluorescent • antibody to detect cytoplasmic • inclusions (Negri bodies).

32. Rhabdovirus Rabies Virus • Preexposure prevention:Rabies vaccine • Postexposure prevention: • Washing wound • Giving rabies immune globulins (passive immunization) into wound • Giving inactivated vaccine (active immunization) made in human cell culture.

33. Hepevirus Hepatitis E Virus • Outbreaks of hepatitis in developing countries. • Similar to hepatitis A virus in the following ways: • - Transmitted by fecal–oral route • No chronic carrier state • No cirrhosis • No hepatocellular carcinoma.

34. Calicivirus Norwalk Virus (Norovirus) • Gastroenteritis (watery diarrhea). • Transmission by Fecal–oral route. • Infection is limited to the mucosal cells of the intestinal tract.

35. Reovirus Rotavirus • Gastroenteritis (diarrhea) in young children. • Rotavirus is resistant to stomach acid • Transmission by the fecal–oral route. • There are two rotavirus vaccines. • Live attenuated vaccine contains single most common rotavirus serotype (G1) • Live reassortant vaccine contains 5 rotavirus strains.

36. Flavivirus Hepatitis C Virus • Hepatitis C & hepatocellular carcinoma. • Transmission is via blood. Sexual transmission & from mother to child probably occurs. • Hepatocellular injury caused by cytotoxic T cells & HCV does not cause a cytopathic effect. • 50% of infections result in chronic carrier which predisposes to chronic hepatitis & hepatocellular carcinoma.

37. Flavivirus Hepatitis C Virus • Serologic testing detects antibody to HCV. • PCR-based assay for "viral load" can be used to evaluate whether active infection is present. • Alpha interferon plus ribavirinmitigates chronic hepatitis but does not eradicate carrier state. • Posttransfusion hepatitis can be prevented by detection of antibodies in donated blood.

38. Deltavirus Hepatitis D Virus • Hepatitis D (hepatitis delta). • Defective virus that uses HBs Ag as its protein coat & replicate only in cells infected with HBV (HBV is helper virus). • Transmitted by blood, sexually & from mother to child. • Hepatocellular injury caused by cytotoxic T cells. • Chronic hepatitis & chronic carrier state occur. • Treatment by Alpha interferon mitigates symptoms but does not eradicate carrier state. • HBV vaccine & HBV hyperimmune globulins will prevent HDV infection also.

39. Retrovirus Human Immunodeficiency Virus • Acquired immunodeficiency syndrome (AIDS). • RNA-dependent DNA polymerase (reverse transcriptase) makes a DNA copy of the genome, which integrates into host cell DNA. • Precursor polypeptides cleaved by virus–encoded protease to produce functional viral proteins. • Antigenicity of gp120 protein changes rapidly • there are many serotypes.

40. Retrovirus Human Immunodeficiency Virus • Transmission by body fluids, e.g., blood & semen, transplacental & perinataltransmission. • Two receptors are required for HIV to enter cells: • 1 - CD4 protein : • it is found on helper T cells. HIV infects and kills helper T cells, which predisposes to opportunistic infections. • 2 - chemokine receptor such as CCR5.

41. Retrovirus Human Immunodeficiency Virus • Detectingantibody with ELISA as screening test and Western blot as confirmatory test. • Determine the "viral load," i.e., the amount of HIV RNA in the plasma, using PCR-based assays. • High viral load predicts more rapid progression to AIDS

42. Retrovirus Human Immunodeficiency Virus • Treatment • Highly active antiretroviral therapy (HAART) consists of two nucleoside inhibitors (inhibit HIV replication by inhibiting reverse transcriptase) & one protease inhibitor (prevent cleavage of precursor polypeptides). • Clinical improvement occurs, but virus persists.

43. Retrovirus Human Immunodeficiency Virus • Screening of blood prior to transfusion for the presence of antibody. • "Safe sex," including the use of condoms. • Nucleoside inhibitors(zidovudine) with or without a protease inhibitor should be given to HIV-infected mothers and their newborns. • Nucleoside inhibitors (Zidovudine & lamivudine) & protease inhibitor should be given after a needle-stick injury.

44. Arboviruses Classification of Major Arboviruses All arboviruses are transmitted by arthropods (arthropod-borne) such as mosquitoes & ticks from the wild animal reservoir to humans.

45. Arboviruses Flavivirus: Yellow Fever Virus • Yellow fever • "Jungle" yellow fever is transmitted from monkeys to human by mosquitoes. • "Urban" yellow fever is transmitted from human (reservoir) to human byAedes mosquitoes • It is severe, life-threatening disease characterized by jaundice & fever. • It begins with sudden onset of fever, headache, myalgias, & photophobia. • There is a live, attenuated vaccine for humans.

46. Arboviruses Flavivirus: Dengue Virus • Dengue fever. • Transmitted by Aedes mosquitoes from one human to another. • Classic dengue (worldwide) (breakbone fever) begins suddenly with influenzalikesyndrome consisting of fever, malaise, cough, & headache. • Severe pains in muscles & joints (breakbone) occur. • Enlarged lymph nodes, maculopapular rash & leukopenia • After a week, symptoms regress but weakness may persist.

47. Arboviruses Flavivirus: Dengue Virus The diagnosis : Isolation of virus in cell culture & Serologic tests that demonstrate presence of: IgM antibody & fourfold or greater rise in antibody titer in acute & convalescent sera. • Outbreaks are controlled by using: • Insecticides • Raining stagnant water serves as breeding place for mosquitoes • Personal protection includes: Using mosquito repellent & Wearing clothing that covers the entire body.

48. Prions • Creutzfeldt-Jakob disease (CJD), variant CJD & kuru (transmissible spongiform encephalopathies) • There is a hereditary form of CJD called Gerstmann-Sträussler-Scheinker (GSS) syndrome. • Prions are composed of protein only. • They have no detectable nucleic acid & highly resistant to UV light, formaldehyde & heat. • They are encoded by a cellular gene.

49. Prions • Pathogenic form (beta-pleated sheet) increases in amount by inducing conformational change in normal form(alpha helix). • In GSS syndrome, a mutation occurs that enhances conformational change to beta-pleated sheet form. • CJD is transmitted by pituitary extracts, brain electrodes & corneal transplants. • Kuruwas transmitted by ingestion or inoculation of human brain tissue. • Variant CJD is transmitted by ingestion of cow brain tissue in undercooked food

50. Prions • Aggregation of prion filaments within neurons occurs, vacuoles within neurons cause spongi-form changes in brain, no inflammation or immune response occurs. • Brain biopsy shows spongiform changes. • Prions cannot be grown in culture.