Infection 4: How do viruses cause disease in humans? Flashcards
Incubation period
From infection to onset of symptoms in primary case
Infectious period
Involves incubation period and symptoms
What is a virus?
Particle made of nucleic acid and a protein coat
Small in size (100x smaller than our cells)
Obligate intracellular- only replicates inside living cells
Can infect wide range of organism
Virus particles
Nucleic acid
- DNA or RNA
- ds or ss
- +/ve/-ve/ambisense
Protein coat
Enveloped/ unenveloped
Nucelocapsid
Nucleocapsid
Nucleic acid and protein coat
Virion
Complete intact virus particle
The physical particle in the extra-cellular phase which is able to spread to new host cells
Viruses which cause encephalitis/ meningitis
JC virus
Measles
LCM virus
Arbovirus
Rabies
Viruses which cause common cold
Rhinovirus
Parainfluenza virus
Respiratory syncytial virus
Viruses which cause pharyngitis
Adenovirus
Epstein-Barr virus
Cytomegalovirus
Viruses which cause gingivostomatitis
Herpes simples type 1
Viruses which cause cardiovascular infection
Coxsackie B virus
Viruses which cause hepatitis
Hepatitis A, B, C, D, E
Viruses which cause skin infections
Varicella zoster virus
Human herpesvirus 6
Smallpox
Molluscum contagiosum
Human papillomavirus
Parvovirus B19
Rubella
Measles
Coxsackie A virus
Viruses which cause eye infection
Herpes simplex virus
Adenovirus
Cytomegalovirus
Viruses which cause parotitis
Mumps virus
Viruses which cause pneumonia
Influenza virus A and B
Parainfluenza virus
Respiratory syncytial virus
Adenovirus
SARS cornoavirus
Viruses which cause myelitis
Poliovirus
HTLC-I
Viruses which cause gastroenteritis
Adenovirus
Rotavirus
Norovirus
Astrovirus
Conoavirus
Viruses which cause pancreatitis
Coxsackie B virus
Problems a virus must solve
Must know what cells to enter and how to enter them
How to replicate inside a cell
How to exit and move from one infected cell to a new cell
Develop mechanisms to evade host defences
Viral pathogenesis
The process by which virus causes disease in a host
Two components of viral disease
- effects of viral replication on the host
- effects of host response on virus and the host
Pathogenesis journey
Encounter
Entry
Multiplication
Spread
Damage
Outcome
Encounter
Virus meets host
Entry
Virus enters host
Multiplication
Virus replicates in the host
Spread
Virus spreads from the site of entry
Damage
The virus, host response or both cause tissue damage
Outcome
The virus or the host wins, or they coexist
Skin
Abrasions
Insect/ animal bites
Needle punctures
Alimentary tract
Gastroenteritis viruses
Movement facilitate viral entry
Hostile environment
- extreme acidity/ alkalinity
- digestive enzymes
Urogenital tract
Mucus membranes; low pH
Abrasions facilitate viral entry
- HPV: local lesions
- HIV: viral spread
Eye
Localised infection- conjunctivitis
Viral spread- eye blindness/ CNS
Viral spread
After replication at site of infection
- some remain localised within epithelium or within one system
- some cause disseminated or systemic infection
Viral release
- apical e.g. flu- facilitate viral dispersal, but virus does no invade underlying tissues
- basolateral e.g. rabies- provides access to underlying tissues and may facilitate systemic spread
Haematogenous spread
Ways of viral entry to blood:
- directly through capillaries
- by replicating in endothelial cells
- through vector bite
- by lymphatic capillaries
Once in the blood, virus has access to almost every tissue
Viraemia
Presence of infectious virus in the blood
- passive/ active viraemia
- primary/ secondary viraemia
Diagnostic value- measuring viral replciation
Practical problem- need to screen blood donors
Neural spread
Less common than haematogenous spread
Viruses can go either way
- from peripheral sites to CNS
- from CNS to peripheral sites
Infection of the CNS
Neurotropic- virus can infect neural cells
Neuroinvasive- virus can enter CNS following infection of peripheral site
Neurovirulent- virus can cause disease of nervous tissue
Tissue tropism
Limited or pantropic
Determinants of tropism
- cell receptors- HIV/CD4+
- cellular proteins that regulate viral transcription- JC/ viral enhancers in oligodendrocytes
- cell proteases- flue/ serine proteases
Viral genes affecting virulence
Those that affect the ability of virus to replicate
Those that modify host’s defense mechanism
Those that enable virus to spread
Those that have intrinsic cell killing effects
Cytolytic viruses
Inhibition of host protein and RNA synthesis leads to loss of membrane integrity
Syncytium formation
Induction of apoptosis
Non-cytolytic viruses
CD8+ mediated
CD4+ mediated
B cell mediated
Chronic/ persistent infection
Continuous replication
Latency- restricted viral gene expression
Latent infection
DNA viruses or retroviruses
Persistence of viral DNA
During cell growth the viral genome is replicated along with the host cell chromosomes
Herpes simplex virus reactivation
Fever, blisters or cold sores
How influenza viruses evade host defense mechanisms?
The virus can change its surface antigens- the immune response no longer able to identify them
Mechanisms of antigenic variation on HA and NA
- antigenic drift
- antigenic shift
