DNA Viruses

• Herpes virus
• Human Papilloma virus
• Hep B (HAV, HCV, HDV)

Herpes Viruses

• Herpes simplex virus (HSV-1 & HSV-2)
• linear dbl-DNA--enveloped virus
• Infection:
  • mucosal (1st)
  • infects neurons
  • reactivation near site of acquisition
• lytic cycle results in damage to ET (1st) or neurons (@ reactivation)

Clinical HSV-1

• most common oral
• cutaneous--herpetic whitlow
• neurological--encephalitis

Clinical HSV-2

• most common genital
• neurological--aseptic meningitis

Nucleoside analogues

• acyclovir
• valacyclovir
• famciclovir

Acyclovir

(ACV)

• prodrug--requiring activation
• converted by viral thymidine kinase to ACV-P
• enzyme converts ACV to ACV-TP
• ACV-TP (active drug)--inhibits viral DNA polymerase

Acyclovir Resistance

• ACV resistance occurs due to mutation in thymidine kinase gene

Acyclovir Uses

• orally against HSV-1-2
• doesn't eliminate but suppresses
• treatment of:
  • herpes genitalis
  • encephalitis
  • varicella (chickenpox)
  • hepes zoster

EBV

• same virology as HSV
• spread by salivary
• occurs among adolescents or young adults

EBV Pathogenesis

• EBV attaches to C3d receptor CD21 on B lymphocytes
  • mount heterophile--IgM
• CD8+ T lymphocytes control infected cells
• latency & reactivation

EBV Clinical

• pharyngeal pain, dysphagia, URI symp, fever
• red throat, purulent exudate, lymphadenopathy, hepatosplenomegaly
• atypical lymphs--heterophile antibody

Varicella Zoster Virus

• primary--chickenpox
• reactivation--herpes zoster
  • dermatomal pattern (shingles)
  • disseminated DZ (pnemonia)
  • encephalitis
• treatment: high dose of nucleoside analogue (acyclovir)

Cytomegalovirus (CMV)

• primary infection--mononucleosis like syndrome
• acquired via oral secretions, breast feeding, sex, blood & organ transplantation

CMV syndromes in AIDS

• CD4<100
• retinitis--visual changes
• esophagitis: pain swallowing
• colitis--diarrhea
• pneumonitis

Ganciclovir given for CMV

• targets CMV DNA polymerase
• phosphotransferase encoded by CMV UL97 gene--> catalyzes GCV to GCV-P
• GCV-TP acts as chain terminator & inhibits CMV DNA polymerase

Ganciclovir Resistance

• genotype UL97 in protein kinase
• 4 to 6 fold increase odds of retinitis progression

HPV

non-enveloped DNA virus

Low Risk HPV

• 6, 11, 42
• skin or mucosal linings
  • warts

High Risk HPV

• 16, 18, 31
• oncogenic potential

anogenital warts

• caused by low risk virus type
  • similar to syphilis

Plantar Warts (HBV)

• 2nd most commmon type of HBV--wart

HPV warts

• podofilox
• imiquimod
• cryotherapy

Squamous Cell carcinoma

HPV-16 & HPV-18

cervical infection w/o visible warts

• no clinical signs of infxn
• atypical squamous cells of undetermined significance (ASCUS) in cytology (PAP)
• colposcopy
  • grading of cells (cervical intraepithelial)
  • neoplasia--staging (oncologist Tumor size--node--metastasis)

HPV Oncogenesis

• HPV induces cells to express host proteins required for viral DNA rep by starting cell cycle progression
• HPV E7--binds retinoblastoma pRB & liberates transcription factor E2F--which drives cell cycle

HPV Oncogenesis

• to prevent cell death HPV E6 protein induces ubiquitination & degradation of tumor suppressor protein p53

Hepatitis A--E (not in this country)

• source: feces
• route: fecal-oral
• not chronic
• pre-post exposure immunizations

Hepatitis B

• source: blood derived
• route: percutaneous permucosal (mom to fetus)
• chronic infection
• pre/post immunizations

Hepatits C

• source: blood derived
• route: percutaneous permucosal
• chronic infxn
• blood donors--IV drug use

Hepatitis D

• source: blood
• percutaneous permucosal route
• chronic infection
• pre/post immunizations

A

• fecal oral spread: hygiene, drug use, MSM, travelers, day care, food
• vaccine preventable

B

• sex transmitted (100x more infectious then HIV)
• blood-borne
• vaccine preventable

C

• blood borne
• 4-5 more common than HIV
• NOT VACCINE PREVENTABLE!!

Hepatitis B virus

• enveloped dbl stranded DNA virus
• circular DNA w/ss-gap
• Family: hepadnaviridae

HBV RX

• peginterferon alfa 2a
• lamivudine

HCV (hep C)

• ss-RNA virus
• family: Flaviviridae
• RNA dependent RNA polymerase--lacks proofreading large # of mutants:
  • quasispecies