NOTES NOTES POLYOMAVIRUS MICROBE OVERVIEW ▪ Small DNA virus → central nervous system, urinary system, skin infection ▪ Poly = multiple, oma = tumor → relationship with multiple tumors ▪ Viral DNA replication, virion assembly occurs inside cell nucleus ▪ Primary infection usually asymptomatic → persistent state Taxonomy ▪ Human polyomavirus species ▫ BK virus ▫ JC polyomavirus ▫ Wu polyomavirus ▫ KI polyomavirus ▫ Merkel cell polyomavirus (MCV) ▫ Trichodysplasia spinulosa virus (TSV) Morphology ▪ Structure ▫ Double-stranded circular DNA ▫ Icosahedral capsid composed of few proteins: VP1 (cell surface binding), VP2, VP3 ▫ Nonenveloped ▪ Non-structural proteins: large, small T antigens ▫ Initiate viral DNA replication ▫ Oncogenic potential Transmission ▪ Probable transmission routes ▫ Fecal-oral, oral, respiratory RISK FACTORS ▪ Immunodeﬁciency BK VIRUS (HEMORRHAGIC CYSTITIS) osms.it/bk-virus PATHOLOGY & CAUSES ▪ Causes hemorrhagic cystitis ▪ BK virus in hematopoietic stem cell transplant recipients → bladder inﬂammation → bladder mucosa bleeding ▪ Primary infection usually asymptomatic/ mild respiratory infection → urinary tract infection → virus in bladder mucosal lining, kidneys 494 OSMOSIS.ORG ▪ Weak immune system → BK viral replication → cells large, round → separate from basal membrane, cell lysis CAUSES ▪ ▪ ▪ ▪ Radiation Chemotherapy Immunosuppressive drugs Urinary tract infection (e.g. BK virus, adenovirus)
Chapter 90 Polyomavirus TREATMENT SIGNS & SYMPTOMS ▪ ▪ ▪ ▪ MEDICATIONS Frequent urination Dysuria Hematuria Suprapubic pain ▪ Mesna, chemotherapy co-administered ▫ ↓ hemorrhagic cystitis risk SURGERY ▪ Cystectomy (severe case) DIAGNOSIS OTHER INTERVENTIONS LAB RESULTS ▪ Polymerase chain reaction (PCR) → infection agent fragments in urine ▪ Urinalysis, cytology ▪ Cystoscopy ▪ Bladder irrigation ▫ Water/sodium chloride solution ▪ Pain management ▪ Hyperhydratation ▪ Hyperbaric oxygen, prostaglandins (↓ efﬁcacy) JC VIRUS (PROGRESSIVE MULTIFOCAL LEUKENCEPHALOPATHY) osms.it/jc-virus PATHOLOGY & CAUSES ▪ Causes progressive multifocal leukoencephalopathy (PML) ▪ Immunocompromised individuals → JC virus → PML (rare demyelinating disease) ▪ Childhood primary asymptomatic infection → latent JC virus in lymphoid organs, kidneys ▪ Immunodeﬁciency → virus spreads via blood → infects brain oligodendrocytes, astrocytes → viral replication → cell lysis → myelin sheath loss ▪ Triggers ▫ Immunosuppressive drugs (e.g. Natalizumab) ▫ Immune system disorders (e.g. HIV/ AIDS) SIGNS & SYMPTOMS ▪ ▪ ▪ ▪ ▪ Cognitive, mental dysfunction Gait, coordination problem Hemiparesis, monoparesis Double/blurred vision Seizure DIAGNOSIS DIAGNOSTIC IMAGING CT scan ▪ Hypodense lesions affect white matter MRI ▪ T1 image decreased signal ▪ T2 image increased signal OSMOSIS.ORG 495
▪ Affects subcortical, periventricular white matter (usually) ▪ Absent contrast enhancement LAB RESULTS Brain biopsy ▪ Large oligodendrocyte nuclei with inclusion bodies ▪ Myelin sheath destruction ▪ Abnormal, enlarged astrocytes ▪ Macrophages engulﬁng myelin ▪ Immunohistochemistry for JC proteins Cerebrospinal ﬂuid (CSF) analysis ▪ PCR detects viral DNA ▪ ↑ white blood cell count (pleocytosis) ▪ ↑ protein level Figure 90.1 An MRI scan in the coronal place of the head of an individual with progressive mutlifocal leucoencephalopathy. TREATMENT ▪ No speciﬁc treatment; high mortality MEDICATIONS ▪ HIV-infected individuals ▫ Start/optimize antiretroviral therapy (ART) ▪ No HIV infection ▫ Stop immunosuppressive therapy ▪ Potentially beneﬁcial drugs ▫ Interleukin-2, cytarabine, chlorpromazine, meﬂoquine OTHER INTERVENTIONS ▪ Natalizumab-caused PML ▫ Plasma exchange 496 OSMOSIS.ORG Figure 90.2 Immunohistochemical staining for JC virus protein in the brain of an individual with progressive multifocal leukoencephalopathy. The protein, stained brown, has accumulated in the oligodendrocytes.