HOW VIRUSES CAUSE DISEASE aka PATHOGENESIS

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HOW VIRUSES CAUSE DISEASEakaPATHOGENESIS

• Development of morbid conditions/of disease
• Cellular events reactions other pathological
  mechanisms occurring in the development of
  disease
• Dorlands Illustrated Medical Dictionary

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HOW VIRUSES CAUSE DISEASE

• Multicellular host v single cell
• Tropism Ability to infect specific cell type
• Viral attachment proteins bind cell receptors
  
• e.g. HIV gp120/T lymphocyte CD4

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VIRUS INFECTION THE MULTICELLULAR HOST

• a) Portal of entry
• b) Target tissue for replication
• c) Portal of exit
• d) Means of transmission

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EPITHELIAL INFECTIONS

• Respiratory e.g. influenza
• RSV (respiratory
• syncytial virus)
• Gastrointestinal e.g. rotavirus
• Genitourinary e.g. papilloma
• Skin e.g. papilloma

7.3.4
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WHY ONLY EPITHELIAL SURFACES?

• Limited virus tropism
• Optimal local temperature
• Polarised virus assembly e.g influenza
• Polarised virus production for release to
  exterior e.g. papilloma virus ? warts

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PAPILLOMA VIRUS REPLICATION

• Basal layer Linked to cell cycle
• Replication as a plasmid
• - no virions
• Granular layer No host DNA synthesis
• Virus replication
• - virions produced

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WHY ONLY EPITHELIAL SURFACES?

• Virus tropism
• Optimal growth temperature
• Polarised virus assembly or production
• Role of host defences

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SUPERFICIAL VIRUS INFECTIONS

• Respiratory Short incubation period
• Intestinal
• Skin Longer incubation period
• Entry, infection disease at same site

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SYSTEMIC VIRUS INFECTIONS

• Disease distant from portal of entry
• Poliovirus - enters via gut
• - disease in central nervous system
• Measles virus - enters via respiratory tract
• - disease is generalised
• ? Longer incubation period

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ROUTES of SUBEPITHELIAL INVASION

• a) Neuronal spread e.g. rabies
• b) Directly to blood e.g. yellow fever
• c) Via lymphatics to blood e.g. polio
• measles

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VIRUS IN BLOOD (VIRAEMIA)

• Free virus eg polio, hepatitis B
• or
• Cell-associated eg measles, HIV

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EXIT PORTAL

• May not be same as entry
• May be multiple

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EXAMPLES OF EXIT PORTALS

• Respiratory tract Influenza, measles
• Oropharynx Herpes simplex
• Alimentary tract Polio virus
• Blood Yellow fever
• HIV
• Hepatitis B

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PATHOGENESIS HOW DISEASE DEVELOPS

• Virus is pathogenic for a particular host if it
  can infect host AND produce disease
• i.e.
• INFECTION DISEASE

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EFFECTS of VIRUSES on CELLS

• Lytic (cytocidal) productive infection, CPE,
  cell death e.g herpes simplex virus (HSV)
• varicella zoster virus (VZV)
• HIV
• Nonlytic (noncytocidal) productive infection BUT
  no CPE or cell death
• e.g. hepatitis B virus (HBV)
• Latent NON-productive infection potentially
  active state but no obvious effect on cell
  function
• e.g. HIV, HSV, VZV

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VIRUS INFECTIONS of THE HOST MAY BE

• Short-lived
• Permanent clearance of initial acute infection
• e.g. influenza, poliovirus
• OR
• Persistent
• Virus persists for a prolonged period (months,
  years) after the first or primary infection
• e.g. HSV, VZV, HBV. HIV

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PERSISTENT VIRAL INFECTIONS

• Latent
• Status of viral genome
• Latent, recurrent activation
• Virus-cell interaction
• Lytic, latent
• Antiviral immune response
• Present, normal

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CHICKENPOX
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PERSISTENT VIRAL INFECTIONS

• 2) Tolerant e.g. HBV neonatal transmission
• Status of viral genome
• Active replication (continuous high level)
• Virus-cell interaction
• Nonlytic
• Antiviral immune response
• Impaired

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PERSISTENT VIRAL INFECTIONS

• 3) Breakthrough e.g. HIV
• Status of viral genome
• Active replication (variable extent)
• Virus-cell interaction
• Lytic, latent
• Antiviral immune response
• Present but virus evades

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EFFECTS of VIRUSES on CELLS

• Lytic (cytocidal)
• Nonlytic (noncytocidal)
• Latent
• Transformation normal cell changed to one with
  potential to become malignant or cancerous cell
• e.g. oncogenic viruses

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CONSEQUENCES OF VIRUS INFECTION FOR
MULTICELLULAR HOST

• Cell death ? tissue injury
• e.g. poliovirus damages CNS
• Excessive immune response
• e.g. EBV in glandular fever/
• infectious mononucleosis
• HBV in adult infection
• Cancer/Oncogenesis
• e.g. HBV

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DISEASE DEPENDS ON HOST STATUS

• Rubella (German measles)
• mother - rash
• fetus - congenital infection
• Herpes simplex virus
• Immunocompetent cold sores
• Immunocompromised - pneumonia
• (Opportunistic infection)

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