1. DNA -VIRUSES
M. Tvorko

3. The Herpesviruses
All members show latency and cause recurrent infection
more severe with advancing age, cancer chemotherapy, or other conditions that compromise the immune defenses
Large enveloped icosahedral dsDNA
Replicates within nucleus

4. Herpesviridae large Family; 8 infect humans HSV-1 HSV-2 VZV CMV EBV
HHV-6
HHV-7
HHV-8

5. Epidemiology of Herpes Simplex Viruses
Transmission
direct exposure to secretions containing the virus
active lesions most significant source
genital herpes can be transmitted in the absence of lesions
HSV multiplies in sensory neurons, moves to ganglia
HSV-1 enters 5th cranial nerve
HSV-2 enters lumbosacral spinal nerve trunk ganglia

6. Epidemiology of Herpes Simplex Viruses
Recurrent infection triggered by various stimuli
fever, UV radiation, stress, mechanical injury
Newly formed viruses migrate to body surface
produce a local skin or membrane lesion

7. Type 1 Herpes Simplex (HSV – 1)
Herpes labialis
fever blisters, cold sores
most common recurrent HSV-1 infection
vesicles occur on mucocutaneous junction of lips or adjacent skin
itching and tingling prior to vesicle formation
lesion crusts over in 2-3 days and heals
Herpetic gingivostomatitis
infection of oropharynx in young children
fever, sore throat, swollen lymph nodes
Herpetic keratitis
ocular herpes

8. Type 2 Herpes Simplex (HSV – 2)
Genital herpes
herpes genitalia
starts with malaise, anorexia, fever, and bilateral swelling and tenderness in the groin
clusters of sensitive vesicles on the genitalia, perineum, and buttocks
urethritis, painful urination
Recurrent bouts usually less severe
triggered by menstruation, stress, and concurrent bacterial infection

9. Herpes of the Newborn HSV-1 and HSV-2
Potentially fatal in the neonate and fetus
Infant contaminated by mother before or during birth
hand transmission by mother to infant
Infection of mouth, skin, eyes, CNS
Preventative screening of pregnant women
delivery by C-section if outbreak at the time of birth

10. Diagnosis, Treatment, and Control
Vesicles and exudate are typical diagnostic symptoms
scrapings from base of lesions showing giant cells
culture and specific tests for diagnosing severe or disseminated HSV
direct fluorescent antibody tests
Treatment
acyclovir, famciclovir, valacyclovir; topical medications

11. Varicella-Zoster Virus (VZV)
virus enters neurons & remains latent
later reactivation of the virus results in shingles with vesicles localized to distinctive areas
dermatomes
treatment
acyclovir, famciclovir, interferon
live attenuated vaccine

12. Epstein-Barr Virus (EBV)
HSV-4
infects lymphoid tissue & salivary glands
transmission
direct oral contact & contamination with saliva
by mid-life 90-95% of all people are infected
causes mononucleosis
sore throat, high fever, cervical lymphadenopathy
Complications include:
heart defects
facial paralysis
rupture of the spleen
jaundice (hepatitis)

13. Epstein-Barr Virus (EBV)
30-50 day incubation
most cases asymptomatic
Burkitt’s lymphoma
associated with chronic co-infections with malaria
nasopharyngeal carcinoma in Chinese & African men

14. Human Herpes Virus 6 HHV-6 T-lymphotropic virus
transmitted by close contact
very common
causes roseola
an acute febrile disease in babies 2-12 months
can cause encephalitis, cancer

15. Human Herpes Virus 6
begins with fever, followed by a faint maculopapular rash
usually self-limited
adults may get mono-like symptoms, lymphadenopathy, hepatitis
over 70% of MS patients show signs of infection

16. Diseases of the Skin Caused by Herpesviruses

17. HEPATITIS B VIRUS:

18. HEPATITIS B VIRUS:

19. HBV SPREAD MAINLY BY PARENTERAL ROUTE
DIRECT PERCUTANEOUS INOCULATION OF INFECTED SERUM OR PLASMA
INDIRECTLY THROUGH CUTS OR ABRASIONS
ABSORPTION THROUGH MUCOSAL SURFACES
ABSORPTION OF OTHER INFECTIOUS SECRETIONS (SALIVA OR SEMEN DURING SEX) 28

20. HBV SPREAD MAINLY BY PARENTERAL ROUTE
POSSIBLE TRANSFER VIA INANIMATE ENVIRONMENTAL SURFACES
VERTICAL TRANSMISSION SOON AFTER CHILDBIRTH (TRANSPLACENTAL TRANSFER RARE)
CLOSE, INTIMATE CONTACT WITH AN INFECTED PERSON 29

21. WHO IS AT GREATEST RISK FOR HBV INFECTION?
LAB PERSONNEL WORKING WITH BLOOD PRODUCTS
SEXUALLY ACTIVE HOMOSEXUALS
PERSONS WITH MULTIPLE AND FREQUENT SEX CONTACTS
MEDICAL/DENTAL PERSONNEL 31

24. Acute Infection HBsAg Anti-HBs Anti-HBc Anti-HBc IgM HBeAg HBV DNA
HBsAg
Anti-HBs
Anti-HBc
Anti-HBc IgM
Months Years
HBeAg
HBV DNA
Anti-HBe
HBV - Diagnosis
Slide 80
Serological Markers of Acute HBV Infection
Incubation period of HBV infection ranges from 60 to 180 days. HBsAg is the first serological marker of acute HBV infection. Early in the course of acute HBV infection, markers of active viral replication (HBeAg and HBV DNA), are also detectable. As the patients recover, serum HBV DNA level markedly decrease but may remain detectable by PCR assay for up to several decades, HBeAg to anti-HBe seroconversion occurs and finally HBsAg becomes undetectable. Persistence of HBsAg for more than 6 months indicates progression to chronic HBV infection.
Anti-HBc IgM is the first antibody to be detected and usually persists for several months. It may be the only marker of acute HBV infection during the ‘window’ period after HBsAg is cleared and before anti-HBs is detected. Recovery from acute HBV infection is indicated by the presence of anti-HBc IgG and anti-HBs.

25. HBV - Vaccine Vaccine Age Group Dose Volume # Doses (ug) (ml)
Engerix-B yr (mo 0,1,6)
 20 yr (mo 0,1,6)
Adults on
hemodialysis (mo 0,1,2,6)
Recombivax HB 0-19 yr (mo 0,1,6)
 20 yr (mo 0,1,6)
(Optional 2-dose) yr (mo 0, 4-6)
hemodialysis * 3 (mo 0,1,6)
Slide 95
Dose schedule of HBV vaccine
Two recombinant HBV vaccines are currently available in the United States: Engerix-B (GlaxoSmithKline Biologicals) and Recombivax HB (Merck & Co., Inc.). The two vaccines can be used inter-changeably. Conventional 3-dose schedules include injections at 0, 1, and 6 months for immunocompetent people.
The dose recommended for children and adolescents is lower while that for immunocompromised adults such as dialysis patients is higher.
In adolescents aged 11 to 15 years, Recombivax HB has been approved for use in a 2-dose, 10ug regimen, with the second dose given 4 to 6 months after the first. This 2-dose regimen should increase compliance and reduce costs.
CDC. Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination: recommendations of the immunization practices advisory committee (ACIP). MMWR 1991;40 (RR-13):1-19.
Koff RS. Hepatitis A, hepatitis B, and combination hepatitis vaccines for immunoprophylaxis. An update. Dig Dis Sci 2002;47:

26. Adenoviruses ADENOVIRUS (1956)
1949. Enders et al.: first cell cultures for cultivation of polioviruses
1953. Rowe et al.: removed tonsills for tissue culture
„blind” passages
cytopathic effect (roundish cells)
normal (healthy) cell culture
AD (Adenoid Degeneration)
APC (Adenoidal-Pharygeal-Conjuctival)
ARD (Acute Respiratory Disease)
RI (Respiratory Illness)
ADENOVIRUS (1956)
adenovirus
virions

27. nonenveloped, ds DNA
30 types associated with human disease
infect lymphoid tissue, respiratory & intestinal epithelia & conjunctiva
oncogenic in animals, not in humans
spread by respiratory & ocular secretions
causes colds, pharyngitis, conjunctivitis, keratoconjunctivitis, acute hemorrhagic cystitis
inactivated polyvalent vaccine
Inclusion bodies

28. VIRION: icosahedral, 80-90 nm
252 capsomers: 12 fibers at the
vertices, 240 hexons,
12 structural proteins (polypeptides)
NUCLEIC ACID: ds DNA
REPLICATION in cytoplasm, virion assembly in the nucleus

31. CLASSIFICATION OF ADENOVIIRUSES
Genera:
Aviadenovirus (birds),
Ataadenovirus (reptiles, ruminants, birds, brush-tail possum)
Siadenovirus (frog, birds)
Ichtadenovirus (new, fish)
MASTADENOVIRUS (vertebrates animals: more than 100 serotypes, 52 human serotypes)

32. MASTADENOVIRUS GENUS
Groups (previosly: Subgenera, grouping based on lenght of
fiber, G/C content of DNA, agglutination of red blood cells (HA),
oncogenicity)
A highly oncogenic (types 12, 18, 31)
B weekly oncogenic (types 3,7, 11, 14,16, 21, 34, 35, 51)
C cell transformation in tissue culture (types 1, 2, 5, 6)
D cell transformation in tissue culture (types 8-10, 13, 15, 17, 19, 20,
22-30, 32, 33, 36-39, 42-50)
E none (type 4)
F ? (types 40, 41)
G (new group) ? (type 52)

33. DIFFERENT SEROTYPES - SAME DISEASE SAME SEROTYPE - DIFFERENT DISEASES
DISEASES CAUSED BY ADENOVIRUSES
DIFFERENT SEROTYPES - SAME DISEASE
SAME SEROTYPE - DIFFERENT DISEASES

34. RESPIRATORY TRACT INFECTIONS:
pharyngitis: types 1,2,3,5,7,
acute respiratory disease of recruits: types 4, 7,14, 21
pharyngoconjunctival fever: types 3,7
pneumonia: 1,2,3,7
pertussis-like syndrome: type 5
EYE INFECTIONS :
pharyngoconjunctival fever (conjunctivitis),
epidemic keratoconjunctivitis: types 8,19,37
(swimming pool, nosocomial: eye droplets,
tonometer) in all age group
follicular conjunctivitis: 3,4,11

35. ENTERIC INFECTIONS: second in
causative agents causing
gastroenteritis in infants (AV types 40, 41,
the first one is rotavirus) and AV type 53 in adults
diagnozis: EM, ELISA or latex agglutination
Urinary tract infections: acute haemorrhagic cystitis: types 11, 21 (children, young adults)
INFECTIONS IN IMMUNO-COMPROMISED PATIENTS: encephalitis,
pneumonia, gastroenteritis, generalized disease (type 5 and new serotypes: 34, 35)
(PREVENTION: „live” adenovirus serotypes 4 and 7 in enterosolvent capsule)

36. RECOMBINANT ADENOVIRUSES (GENE THERAPY)
DNA
Introduction of foreign genes
(malignant diseases, diseases
based on gene defects)
immune therapy (cytokin genes),
moleculare therapy (tumor
suppressor genes),
virus therapy

38. PARVOVIRUSES Parvus: very small VIRION: icosahedral, 20-25 nm
NUCLEIC ACID: (-) DNA
REPLICATION: in the nucleus, with
the help of cellular enzymes
CLASSIFICATION:
Family: PARVOVIRIDAE
Subfamily: PARVOVIRINAE
Genera:
ERYTRHOVIRUS (B19)
Bocavirus (human bocavirus)
Parvovirus (RA-1)
Dependovirus (requires helper virus :
AAV, Adenovirus Associated Virus)
Densovirus (animal pathogens)
adenovirus
AAV

39. ERYTHEMA IINFECTIIOSUM
„FIIFTH DIISEASE”
(morbiillllii,, chiickenpox,, rubelllla,, scarllet fever )
• Human parvovirus B19 (respiratory
droplets, seasonality: autumn,
winter, high % of seropositivity)
• special affinity to red blood cells (haematological changes)
• severe situation in chronic anaemia
• in pregnancy: spontaneous abortion, malformations

40. Papillomavirus papilloma caused by 100 different strains of HPV
benign, squamous epithelial growth, wart or verruca
caused by 100 different strains of HPV
common seed warts
Fingers
plantar warts
soles of feet
genital warts
prevalent STD
transmissible through direct contact or contaminated fomites
Incubation
2 weeks – more than a year

41. Genital Warts most common STD in US over 6 M new cases each year
30 M carriers of one of the 5 types of HPV associated with genital warts
strong association with cervical & penile cancer
type 16 & 18
Treatment
podophyllin chemical treatment, cauterization, freezing, laser surgery, immunotherapy