• exposure
• incubation periods
• prodromal illness
• clinical illness (infection may be asymptomatic)

• exposure
• attachment
• host cell entry, viral uncoating
• primary replication and release
• lateral spread in tissue
• systemic spread to target tissue
• tissue tropism
• evasion of host immune response

• exposure and mode of spread within the body
• immune response and viral counter response
• tissue tropism

• inhalation of respiratory aerosol dropletes
• cough generate many aerosole particles, but the most generated by a sneez
  • if less than or equal to 5 microns, particles may reach alveoli
  • more than 5 microns, particles trapped by nasal mucosa
• oropharynx and nasopharynx can be a portal of entry

• ingestion of fecally contaminated food/water
• bile salts remove lipid envelope
  • GI entry limited to non enveloped virus
• partial proteolysis may enhance infectivity
• invasion facilitated by M cells in Peyer's patch

• direct exposure/penetration
  • mucosal surfaces
  • penetrating injury
  • vecgtor
• outcome of exposure depends on:
  • pathogen
  • inoculum size
  • host immune system
• transplacental or vertical

• basolateral- may faciliate viral access to lymphoid, neural, or vascular structures
• apical- may facilitate localized spread

• localized
  • spread via diffusion of released virus; increased by fluid layer
  • lateral spread in epithelium via cell fusion
    • viral Ag on host cell surface may trigger cell fusion leading to giant cells or syncytia
    • allows cell to cell spread and avoid host Ab
• lymphatic spread
• neural spread
  • intraneuronal, fast axonal transport
  • slow axonal transport

• free virus
• cell associated (ex: macrophages, lymphocytes)

• route of entry or extent of spread
• tissue specific cellular receptors
• cell or tissue specific viral enhancers, promoters
• temperature

• preferential viral protein synthesis
• block cellular DNA, mRNA synthesis
• block export of mRNA from nucleus
• block cellular protein synthesis
• viral mRNA may compete for ribosomal sites
• synthesis DNAase to provide substrates for viral genome replication

• made via:
  • virus induced changes in membrane or chromosomal structure
  • may represent collections of viral particles or capsids
• types
  • cytoplasmic
  • intranuclear

• inhibition of normal cellular processes
• accumulation of viral proteins
• loss of membrane integrity
• viral Ag expression
  • may target host cell for immune cytolysis
  • may lead to cell fusion, syncytia formation

• nonspecific
  • IFN, NK cells, macrophages
• Ab
  • neutralizing Ab block infection
  • kill infected cells via complement activation
• cell mediated immunity
  • required for cell lysis in nonlytic infection
  • required for neutralization of enveloped viruses

• active at very low levels to viral infection or dsRNA
• actions
  • induce synthesis of cellular proteins that minimize viral replication
  • phosphorylation/inactivation of protein synthesis initiation factor and inhibit viral protein synthesis
  • activation of cellular RNAases that degrade viral mRNA
  • increase NK cell, cytotoxic T cell, and ADCC activity

if cell lacks MHC I, it will kill it

1. Ab binding
2. binding of complement
3. form proteolytic complex
4. C5b binds and forms MAC to kill virus

• inhibition of IFN action
• decrease cytokine production
• suppress MHC expression
• reduce B cell activation
• antigenic variation
• immunologic sanctuaries
• latent infection

• immunocytolysis- direct cell damage
• cross reacing Ab may damage host tissue
• immune complex deposition on BM
  • complement activation
  • local release of inflammatory mediators
• CD4 induced delayed type HS
• superAg binding- massive cytokine release
• cellular transformation

1. uncontrolled cell growth
2. continued growth without senesence
3. increase rate of cell growth
4. loss of contact inhibition of cell growth
5. accumulation of tumorigenic mutation

• dx
• selection of tehrapy
• design of new therapies
• resistance testing
• understanding viral pthogenesis
• understanding eukaryotic host cell biology

• clinical
• pathologic (scrape off vesicle, do a Giemsa stain)
• tissue culture
• immunologic
• biochemical
• ultrastructural

• vacuolation
• giant cells, syncytia formation
• rounding
• cellular inclusions

• detection of virus specific Ab
  • neutralizing Ab
  • ELISA
  • complement fixation
  • hemagglutination inhibition
• detection of viral Ag
  • immunofluorescence
  • radioimmunoassay
  • ELISA
  • Western blotting

• undiluted serum forms immune complexes
• diluted serum (Ag excess) is unable to form complexes

• determine specific Ab titer
  • test serial 2 fold dilutions of serum
  • titer is highest Ab dilution that give a rxn
• active infection
  • IgM Ab response = acute infection
  • 4 fold rise or fall in IgG titer = acute infection
• past infection= single IgG titer

1. take serum and take artifically synthesized Ag from virus of interest add to solid medium
2. if Ab to Ag, they will bind to it
3. wash away
4. get anti-Ab, and if they bind to primary Ab is stuck, they will bind and convert substrate to fluorescent molecule

• nucleic acid hybridization
• PCR
• DNA/RNA sequencing
• enzyme assays
• protein electrophoresis

1. separating DNA fragments blotted onto nitrocellulose paper
2. labeled DNA probe hybridized to separated DNA
3. labeled DNA probe hybridized to complementary DNA bands visualized by autoradiography