1. بسم الله الرحمن الرحيم 1 1 1

2. Classification of DNA Viruses
Virus Family
Envelope Present
Capsid Symmetry
DNA Structure
Medically Important Viruses
Parvovirus No
Icosahedral
SS, linear
B19 virus
Polyomavirus
DS, circular, supercoiled
JC virus, BK virus
Papillomavirus
Human papilloma virus
Adenovirus
DS, linear
Hepadnavirus
Yes
DS, incomplete circular
Hepatitis B virus
Herpesvirus
Herpes simplex virus, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus
Poxvirus
Complex
Smallpox virus, molluscum contagiosum virus
1SS = single-stranded; DS = double-stranded.

3. 1-Herpesviruses Virus Primary Infection Usual Site of Latency
Recurrent Infection
Route of Transmission
HSV-1
Gingivostomatitis
Vesicular lesions above the waist
Cranial sensory ganglia
Herpes labialis, encephalitis, keratitis
Via respiratory secretions, direct contact with virus vesicle & saliva
HSV-2
Herpes genitalis
Vesicular lesions below the waist
Perinatal disseminated disease
Lumbar or sacral sensory ganglia
Sexual contact, perinatal infection
VZV
Varicella
Initial infection in oropharynx.
It spreads via blood to liver then to skin.
Cranial or thoracic sensory ganglia
Zoster
reactivate years later, in older and immuno-compromised individuals.
Via respiratory secretions

4. Via respiratory secretions & saliva Sexual or organ transplantation
1-Herpesviruses
Virus
Primary Infection
Usual Site of Latency
Recurrent Infection
Route of Transmission
EBV
Infectious mononucleosis
It start in pharyngeal epithelium, spreads to cervical lymph nodes, then travels via blood to liver & spleen.
B lymphocytes
None
Via respiratory secretions & saliva
CMV
Congenital infection (in utero)
Mononucleosis in transfusion recipients.
Pneumonia & hepatitis in immuno-compromised patients
Retinitis & enteritis, in AIDS patients
Uncertain
Asymptomatic shedding
Dissemination in immuno-compromised patients
Intrauterine infection
transfusions,
sexual contact, & secretions
HSV-8
Kaposi's sarcoma
in AIDS patients
Sexual or organ transplantation

5. 1-Herpesviruses
Herpes viruses-1

6. Herpesviruses
Varicella viruses

7. Herpesviruses
Zoster viruses

8. Herpesviruses
Epstein-Barr virus

9. Adenovirus
Upper & lower tract respiratory disease (pharyngitis & pneumonia).
Enteric strains 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 into hepatocyte 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 months chronic carrier.
Presence of e antigen infectious 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 & lamivudine reduce 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 Medically Important Viruses
Virus Family
Envelope Present
Capsid Symmetry
RNA Structure
Medically Important Viruses
Picornavirus No
Icosahedral
SS linear,
nonsegmented,
positive polarity
Poliovirus
Rhinovirus
hepatitis A virus
Hepevirus
SS, linear
non-segmented
Hepatitis E virus
Calicivirus
Norwalk virus
Reovirus
DS linear, 10 or 11 segments
Rotavirus
Flavivirus
Yes
Yellow fever virus,
dengue virus
West Nile virus,
hepatitis C virus
Togavirus
Rubella virus

16. Classification of RNA Viruses
Virus Family
Envelope Present
Capsid Symmetry
RNA Structure
Medically Important Viruses
Retrovirus
Yes
Icosahedral
SS linear, 2 identical strands (diploid), positive polarity
HIV
human T-cell leukemia virus
Orthomyxovirus
Helical
SS linear, 8 segments, negative polarity
Influenza virus
Paramyxovirus
SS linear, nonsegmented, negative polarity
Measles virus,
mumps virus,
respiratory syncytial virus
Rhabdovirus
Rabies virus
Filovirus
Ebola virus
Marburg virus

17. Enteroviruses: Poliovirus
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. Enteroviruses: Poliovirus
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. Enteroviruses: Poliovirus
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. Enteroviruses: Hepatitis A Virus
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 cytopathic for hepatocyte & hepatocellular injury is caused by immune attack by cytotoxic T cells.
Vaccine contains killed virus. Administration of immune globulin during incubation period

21. Enteroviruses:Coxsackie Viruses
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
Transmission by 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. Orthomyxovirus Influenza Virus
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) & Zanamivir is 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 secretory IgA, 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. Respiratory Syncytial Virus
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 Transmission by respiratory droplets.
Common cold & SARS (severe acute respiratory syndrome).
Transmission by respiratory droplets.
It Infects mucosal cells of respiratory tract.

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. Norwalk Virus (Norovirus)
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 ribavirin mitigates 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. Human Immunodeficiency Virus
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. Human Immunodeficiency Virus
Retrovirus
Human Immunodeficiency Virus
Transmission by body fluids, e.g., blood & semen, transplacental & perinatal transmission.
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. Human Immunodeficiency Virus
Retrovirus
Human Immunodeficiency Virus
Detecting antibody 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. Human Immunodeficiency Virus
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. Human Immunodeficiency Virus
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. Classification of Major Arboviruses
Family
Genus
Viruses of Medical Interest
Togavirus
Alphavirus
Eastern equine encephalitis virus
western equine encephalitis virus
Flavivirus
St. Louis encephalitis virus
Yellow fever virus
Dengue virus,
West Nile virus
Bunyavirus
California encephalitis virus
Reovirus
Orbivirus
Colorado tick fever virus
All arboviruses are transmitted by arthropods (arthropod-borne) such as mosquitoes & ticks from the wild animal reservoir to humans.

45. Flavivirus: Yellow Fever Virus
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 by Aedes 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. Flavivirus: Dengue Virus
Arboviruses
Flavivirus: Dengue Virus
Dengue fever.
Transmitted by Aedes mosquitoes from one human to another.
Classic dengue (worldwide) (breakbone fever) begins suddenly with influenzalike syndrome 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. Flavivirus: Dengue Virus
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.
Kuru was 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.