Untitled Quiz

Neurotropic Viruses

Rabies (Rhabdovirus) is an acute, fatal CNS infection spread by rabid animal bites.
The classification includes:
- Family: Rhabdoviridae
- Genus:
  - Lyssavirus (rabies lyssavirus)
  - Vesiculovirus (vesicular stomatitis-like virus)
Morphology: bullet-shaped particles, ~75 x 180-200 nm
Contains:
- ss (-)sense RNA and RNA-dependent-RNA-polymerase in the virions.
- GP (10 nm) covered super capsid - contains cylindric nucleocapsid.
Antigenic structure:
- One serotype, various strains
- Encodes 5 proteins/antigens:
  - G - glycoprotein receptors, associated in trimers and forms the surface peplomeres that binds to human receptors to facilitate receptor-mediated endocytosis
  - M - matrix antigen, facilitating successful budding within the capsid,
  - N - nucleoproteins, main nucleocapsid component, providing bases for polymerase,
  - L - RNA-dependent-RNA-polymerase,
  - P - cofactor for polymerase

Slow Viral Infections

Slow viral infections (SVIs) - chronic degenerative infectious diseases of the central nervous system (CNS).
Characteristics:
- Incubation period up to 5 years
- Slow progression of clinical manifestations (chronic infections)
- Progressive degenerative changes (not inflammation)
- Resulting death
Causative Agents:
- Viruses (typical agents)
- Prions (unconventional agents)
Viral-caused:
- Subacute sclerosing panencephalitis (SSPE):
  - Slowly progressive demyelination in CNS
  - Rare in teens/young adults
  - Occurs 7-10 years after measles
  - Defective measles viruses, mutation in one or more proteins
- Progressive Multifocal Leukoencephalopathy (PML):
  - Caused by reactivation of JC virus
  - CNS complication in immune-compromised individuals
  - Leads to demyelination in the CNS

Oncogenic Viruses

Oncogenic viruses cause malignant processes in cells
Cancer origin theories:
- Viruses
- Chemical
- Physical
Example of a virus-induced cancer in the 20th century:
- 1908, Ellerman and Bang - leukemia can be transferred with cell-free tissue filtrates
- 1912, Rous - Rous sarcoma virus (RSV)
- 1933, Shope - papilloma virus
- 1951, Gross - leukemia virus
- 1957, Stewart - polyomavirus
General characteristics:
- 100+ known oncogenic viruses
- Koch's postulates cannot be used in human oncogenic viruses because a host determines the oncogenicity of the virus.
Cell transformation characteristics:
- Change morphology
- Change metabolism (rapid division)
- Non-fastidious in cultures
- Chromosome aberration in cells
- Specific tumour Ag expression
- Tumours develop upon infusion in animals
DNA-viruses:
- Papillomaviruses (HPV)
- Human papillomavirus (HPV) causes benign verruca vulgaris and more malignant manifestations such as laryngeal papilloma, condyloma acuminata, cancer of the uterine cervix, epidermodysplasia etc.
- Polyomaviruses - JC and BK viruses which can lead to Merkel cell carcinoma, Vacuolating virus SV40
Herpesviruses (HSV)
- Epstein-Barr virus (EBV)
- EBV may cause malignant lymphomas, nasopharyngeal carcinomas, and infectious mononucleosis
- Epstein-Barr virus (EBV) can cause various clinical manifestations as it causes gene translocations instead of directly causing malignancy
Other viruses
Adenoviridae
Hepadnaviridae (hepatitis B virus)
Poxviridae
RNA viruses:
- Retroviridae
  - Oncovirinae (HTLV-1, HTLV-2, HTLV-5)
  - Lentivirinae (HIV-1, HIV-2)
  - Spumavirinae

TBE: Tick-Borne Encephalitis

A tick-borne encephalitis virus (caused by a Flavivirus)
Source: infected ticks (can be infected at any stage)
Transmission:
- Transovarially
- Milk of infected goats for long periods
Incubation period: 10-12 days (range 1-40 days)
Pathogenesis: virus multiplies in non-neural tissues → blood (viremia) → tropism to CNS
Clinical findings: diphasic course
- First phase: influenza-like symptoms
- Second phase in 35% of cases: meningitis/encephalitis/myelitis, with or without paralysis
Clinical forms:
- Mild, (3-5 weeks)
- Medium severe (6-8 weeks)
- Severe (paralysis, mortality <20%)
Viral clearance rates up to 65% of infected individuals.

Slow Virus Infections - Caused by unconventional agents

Prion-caused diseases
- Characteristics
  - Confined to the CNS
  - Progressive vacuolation in neurons
  - Extensive astroglial hypertrophy
  - Amyloid plaques present
  - Long incubation period
  - Chronic progressive pathology
  - Always fatal
- Human diseases:
  - Kuru
  - Creutzfeldt-Jakob disease (CJD)
  - Gerstmann-Sträussler-Scheinker syndrome (GSS)
  - Fatal familial insomnia (FFI)
- Animal diseases:
  - Scrapie of sheep (goats)
  - Transmissible encephalopathy of mink
  - Bovine spongiform encephalopathy (BSE) ("Mad Cow Disease")
  - Chronic wasting disease (mule, deer, elk)
Characteristics of prions: - Unusual resistance to standard means of inactivation (resistant to formaldehyde, ethanol, proteases, ionizing radiation, ↑t°) - Sensitive to phenol (90%), house bleach, ether, acetone, strong detergents, iodine disinfectants, autoclaving - Long doubling time of at least 5.2 days - No CPE in vitro - Long incubation period (~30 years) - Causes vacuolation of neurons (spongioform), amyloid plaques, gliosis - Symptoms that include problems with muscle control, shivering, tremors, dementia - Lack of antigenicity and immunogenicity - Lack of inflammation - Lack of IFN production
Mechanism of prion diseases:
- The aberrant PrPsc is sufficient to cause disease.
- PrP binds to normal PrP causing it to be processed into PrPsc and released. The cell replenishes the PrP. This cycle continues.
- Gene mutations – can cause normal PrP to become PrPSc.