M. Tvorko

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

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

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 5 th cranial nerve – HSV-2 enters lumbosacral spinal nerve trunk ganglia

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

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

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

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

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

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

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)

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

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

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

Diseases of the Skin Caused by Herpesviruses

HEPATITIS B VIRUS:

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)

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

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

HBV - Diagnosis Acute Infection HBsAg Anti-HBs Anti- HBc Anti-HBc IgM Months Years HBeAg HBV DNA Anti-HBe

HBV - Vaccine VaccineAge GroupDose Volume# Doses (ug) (ml) Engerix-B 0-19 yr (mo 0,1,6)  20 yr (mo 0,1,6) Adults on hemodialysis (mo 0,1,2,6) Recombivax HB0-19 yr50.53 (mo 0,1,6)  20 yr (mo 0,1,6) (Optional 2-dose)11-15 yr (mo 0, 4-6) Adults on hemodialysis401.0 * 3 (mo 0,1,6) VaccineAge GroupDose Volume# Doses (ug) (ml) Engerix-B 0-19 yr (mo 0,1,6)  20 yr (mo 0,1,6) Adults on hemodialysis (mo 0,1,2,6) Recombivax HB0-19 yr50.53 (mo 0,1,6)  20 yr (mo 0,1,6) (Optional 2-dose)11-15 yr (mo 0, 4-6) Adults on hemodialysis401.0 * 3 (mo 0,1,6)

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

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

VIRION: icosahedral, 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

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)

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)

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

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

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)

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

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) VIRION: icosahedral, nm adenovirusAAV PARVOVIRUSES Parvus: very small

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

Papillomavirus papilloma – 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

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