Lecture 3

Pathogenesis
- virus- cell interactions
- in permissive cells -> productive infections with virion production
- cytolytic infection -> lysis of the cell
- non-cytolytic infection -> virus release by budding, may lead to persistent infection (co-
existence of cell and virus)
- in non permissive cells
- abortive (non productive) -> resistant cells (no absorption of the cell) or infection of cell but
no virus production
- virus enter cell and insert DNA, but are not produced
- Latency -> presence of the virus in genome form, but no expression of viral genes, the
genome is maintained throughout cell devision (more common with DNA virus, e.g.
herpes virus)
- Transformation -> change of properties (tumour cells) but transformation only in 1 in
10^5 cells, DNA viruses: adenoviruses, herpesviruses, hepadnaviruses,
papillomaviruses, poxviruses; RNA viruses: retroviruses
- virus- host interactions
- types
- acute: short duration (several days)
- latent: recovering from initial infection but persistent and possible recurrence of the virus
(hidden in cryptic form)
- chronic: detectable for a long period of time (asymptomatic carrier state or chronic illness)
- slow viral infections: prolonged period between initial infection and appearance of disease
(e.g. SSPE or prion infection)
- stages
- incubation: asymptomatic
- prodrome: nonspecific symptoms
- specific period: specific symptoms
- recovery: resolving of illness
- persistence of infection, carrier state or latent infection
- population
- sporadic: few, unrelated cases
- endemic: constant rate of cases in a defined area
- epidemic: increase in number above a baseline
- pandemic: spreading across continents
- morbidity: frequency of disease
- incidence: new cases in 100000
- prevalence: all cases in 100000
- mortality: frequency of fatal cases
- pathogenesis:
 - cell killing due to viral replication (e.g. polio kills motor neurone -> paralysis
- immune response: cytotoxic T cells (e.g. hepatitis A,B,C), virus-antibody-complement
deposited in tissue
- pathogenic agent:
- capable of causing the disease
- property of a species
- cannot be measured
- virulence
- ability to cause disease
- property of viral strain
- can be measured
- increase or decrease
- attenuated viruses lost virulence
- stages of pathogenesis
- transmission
- horizontal -> person to person (direct: body fluids, indirect: contamination)
- vertical -> mother to offspring (transplacental, during delivery, during breast feeding)
- zoonotic (direct bite from animal reservoir, insect vectors transfer from animal reservoir
to human)
- portal of entry
- skin
- papillomaviruses - injuries
- flavivirdae - vectors
- rabies virus - direct bite
- needles (blood) - hepatitis B, C, D , HIV
- respiratory tract - respiratory secretions
- Influenzavirus
- Rhinovirus
- Respiratory syncytial virus
- Herpes virus (herpes simplex, Epstein-Barr, cytomegalovirus, varicella- zoster)
- Measles virus
- Mumps virus
- Rubella virus
- Hantavirus
- Adenovirus
- GI tract
- GI tract infections: adenovirus and rotavirus
- systemic infections: Hepatitis A, enteric viruses, poliovirus)
- anus: HIV, human papilloma virus
- Genital tract
- papillomavirus
 - Hepatitis B virus
- HIV
- Herpes simplex virus 2
- conjunctiva - adenovirus
- transplacental
- cytomegalovirus
- Rubella virus
- Herpes simplex virus
- Herpes zoster virus
- Hepatitis B
- HIV
- Parvovirus B19
- virus can be localised to portal of entry
- common cold: influenzavirus, rhinovirus, coronavirus
- Rotavirus - enteric disease
- papilloma viruses: warts, cervical cancer
- systemical spread: e.g. polivirus
- spread through bloodstream (viraemia), lymphatic system, nerves, epithelial cells
- macrophages usually inactivate virus, but HIV can multiply inside of infected
macrophage, which may distribute the virus through the body
- tropism: the range of cells a virus can infect, determined by receptors and coreceptors
- Elimination:
- skin lesions -> Herpes simplex virus, papillomaviruses
- respiratory tract secretion
- saliva -> mumps, Epstein Barr, rabies
- faeces -> enteric viruses, Rotavirus, hepatitis A
- urine -> adenovirus
- genital secretions -> HIV, hepatitis A, B , papillomavirus, herpes simplex virus 2
- milk -> human T-cell lymphotropic virus (HTLV)1, HIV, cytomegalovirus
- blood -> hepatitis B, C, cytomegalovirus, Epstein-Barr, HIV, HTLV 1, arborvirus