Pathogenesis Flashcards
Def. pathogenesis, disease, virulence
Pathogenesis: entire process by which viruses cause disease
Disease: harmful pathologic consequence of infection
Virulence: relative capacity of pathogen to cause disease
Outcomes of infection
Productive: new infectious virus produced
Abortive: enters host but no infectious virus produced
Latent: no infectious virus detectable but can be reactivated
Def. susceptible, permissive, cell tropism
Susceptible: cells in which virus can enter, unclear if subsequent steps of viral replication can proceed
Permissive: steps in which all steps of viral replication can proceed
Cell tropism: spectrum of cells/cell lines that can be infected by virus
Requirements for starting infection
Sufficient viral particles must be transmitted.
Cells at site of infection must be accessible, susceptible and permissive.
Antiviral responses must be absent or insufficient.
Portals of entry
Conjunctiva, alimentary tract, respiratory tract, urogenital tract, capillaries etc
Protection of respiratory tract
Mucus, ciliary movement and macrophages protect respiratory tract against infection.
Infection of respiratory tract, NA?
Infected part determines disease.
Antiviral defenses.
Neuraminidase facilitates mucus penetration by destroying sialic acid.
How does NA promote virus infection?
Promotes viral release from infected cells.
Allows virus to penetrate mucus.
Def. local/disseminated/systemic infection
Local: spread limited to site of entry
Disseminated: spread beyond site of entry
Systemic: spread to several organs
Viral release in polarized cell - consequence?
Site of release can determine whether virus spreads locally or is disseminated.
Apical: local
Basolateral: disseminated
(determinant of release: GP sorting)
Neuronal vs hematogenous spread
Viruses can use blood/lymph (Measles, Mumps) or neurons (Herpes, Rabies) for dissemination.
Neurotropic, - invasive, -virulent
Neurotropic: can infect neuronal cells
Neuroinvasive: can enter CNS
Neurovirulent: can cause disease of nervous tissue
Invasion of organs detemrined by…
..properties of the endothelium (continuous/fenestrated/sinusoid with macrophages)
Viral trojan horses
Cells can ferry the virus from sites of entry to target organs:
Eg HIV > transported by DCs to lymphoid tissues
Methods to analyze pathogenesis
Monitor patients.
Experimental infection of animals.
Histopathology.
Detection of viral spread
Reporter proteins: virus wiht integrated luciferase gene > quantify infection as intensity of luciferase signal
Which processes can be determined by cytoplasmic tail of viral GPs?
Site of virus budding.
Virion incorporation
Required host cell factors
Receptors, regulators of transcription, cellular proteases.
Determinants of viral tropism
Receptor expression, transcription factors, proteases
Host defense
Anatomical/chemical barriers, intrinsic (eg restriction factors) / innate (IFN, NK) / adaptive/immunity
Determinants of infection outcome
Amount of virus transmitted, kinetics of antiviral response
Viral receptors..
Bound by viral GP for host cell entry.
Determine viral tropism.
Coronaviruses
Enveloped. (+) RNA genome.
Envelope, membrane, spike protein.
Alpha/Beta/Gamma genera.
Corona virus zoonosis
SARS: bat is natural reservoir, civet cats/racoon dogs are intermediate hosts
MERS: related viruses in bats > now dromedary camels are natural reservoir
SARS-CoV2: unclear, bats?
How is transmission efficiency of SARS determiend?
Interaction of SARS spike with ACE2.
SARS immune response
Dysregulated/delayed IFN and inflammatory responses.
(robust or no IFN response > mild disease)
IFN recruit monocytes/macrophages > dyregulated cytokine produciton, uncontrolled apoptosis
Coronavirus species?
SARS/-2, MERS: highly pathogenic
229E, NL63, OC43, HKU1: common cold
Cytokine storm in other diseases
Ebola
Influenza
Determinants of cross-species transmission/pathogenessis of coronaviruses
Interaction of viral spike protein with cellular receptors.
Bats can serve as reservoirs.
Modulaiton of IFN/cytokine expression promotes pathogenesis.
