Lec 16 Viral pathogenesis Flashcards
Patterns of Viral Infection
What is a Fomite?
Host nutrition and immunity, age, gender, stress!
Virus (quasi) species and strain
FOMITE: INANIMATE OBJECT that CARRIES PATHOGEN
Environment: vaccine, government
Infection does NOT ALWAYS MEAN DISEASE
Productive infection: INFECTIOUS VIRUSES are produced, equilibrium infection
ABORTIVE: no new viruses made, non-equilibrium, body will kill virus or vice versa :(
Acute: either host OR disease will die => non equilibrium: the body and virus fight for their lives. Can lead to chronic infection.
Chronic infection => equilibrium. Persistent, latent infections. Continuous viral replication, latency and reactivation. eg. HSV (Herpes)
The IS responds differently to acute and chronic infections! eg. cytokine interferon gamma only works on chronic mice brain infections, not acute.
“Failure to clear all evidence of infection symptom examples:” vomitting, diarrhea
Chronic Infection
Chronic Infection: latency for a long time and continuous infection.
Virus continues to make new virus particles despite the host response, which is not strong enough to target or subdue virus, or too compromised to act effectively against it. Depends on virus… complications vary very widely.
All host cells will become infected by heavily infectious virus like HIV and HSV.
LATENCY: virus particles will REPRODUCE WHEN REACTIVATED. When virus particles are not produced the virus is invisible.
Mono: Epstein-Barr V works during ACUTE infection to target MEMORY B CELLS
Disease and Virulence
Virulence impacts on host
Disease is always caused by infection
infection does NOT always cause disease.
Sometimes disease symptoms are specific to tissue/organs while sometimes they are not…
Virulence: ability to cause infection, which causes the disease. Often VIRULENT VIRAL DISEASES are SEVERE. Depends on:
- INVADE cells
- INFECT cells
- EVADE IS
- Cause tissue DAMAGE
Virulence genes,
viral proteins,
virulence determinants (not coded by viruses, not aways encoding proteins! eg. viral envelope resistant to host control protein)
Invasiveness and Evasion
INVASIVENESS: ability to ENTER and DAMAGE HOST TISSUES
Evasion: ability of virus to avoid detection and response by host immune system
- viruses have genes that encode proteins that mimic host proteins
- virus gene products mutate so they are not influences by Ab
Different for acute and chronic aversion.
Subversion
SUBVERSION: Virus CHANGES some INTERCELLULAR PROCESSES so viral gene expression is not hurt, or the virus is not killed.
eg. Change chemokine signalling receptors, which would otherwise signal the IS to kill the cell (displaying foreign antigens on it)
Reoviruses
JAM1
Reoviruses are dsRNA viruses
that attach to epithelial cell JAM1 host adhesion molecule above aggregate of immune cells.
Virus is proteolysed and cause conf. change to become ISVP (Infectious SubViral Particle) and
invade M CELLS, which are
ABOVE PEYER’S PATCHES and
HURT LYMPH NODES
Stages of Poliovirus Infection
phases 1 and 2
p2 conclusions
Phase 1. POLIOVIRUS (PICORNAviridae, +ssRNA)
a)invades intestines through ORAL,
b) binds to M cells of PEYER’s patches,
c) REPLICATES in LYMPHOID Cells
results in PRIMARY VIREMIA (viral particles in blood)
Phase 2. LYMPH cells MIGRATE
a) replicates in secondary sites, causes secondary viremia
b) EVENTUALLY gets to BLOOD: BRAIN BARRIER
The IS fires a response. There are 2 outcomes:
1) Host wins: Host Abs PREVENT Viral spread to CNS and motor neurons.
2) Virus wins: Viral particles beat the host to the CNS and motor neurons, which becomes DYSFUNCTIONAL, causing PARALYSIS!
Infectious Bottleneck
Because pathogenesis causes the RANDOM MUTATIONS in viral particles, quasi species are formed, influenced by host selective pressures.
These quasi species become specific for the tissues they replicate inside. The IS is not competitively strong enough against this…
Allelic Variation among Hosts
Alleles of the same gene participate in the bottleneck effect to cause a larger number of quasi species.
eg. in HIV it begins by targeting CCR5 receptors but moves into CXCR4 receptors b/c the body removes the virus easily from CCR5. CXCR4 still help the virus spread, but is slower.
Inflammation
Inflammation is caused by infected cells and/or the virus.
Some cells burst b/c they attract cytokines, which kill the cell, even though they are no infected by viruses.
Viral diseases can develop w/o inflammation too
eg. SINDBIS virus (togaviridae, +ssRNA) infects baby mice and causes paralysis. Does not infect older mice though, so host factors are also important.
Tropism
Walking dead: brain
6 tissues of entry
Skin: great barrier
Blood: balance between vehicles used, clearance, access to blood
Lymphoid tissues: attack the immune cells b4 they respond
Host cell receptors: PRIMARY DETERMINANT of virus distribution within tissues
DIC: Disseminated Intravascular Coagulation: swelling of the tongue, elephant dead
Long living cells become reservoir for viruses b/ they have specific properties that help or inhibit virus infection and replication at different cell stages
Tropism and Tissue Distribution
a
Immuno privileged Sites
IS has selective ability to clear certain virus from certain tissues
eg. CD8 T cells eliminate infection from MHC 1 hepatocytes.
LCMV causes persistent infection in a few places the IS cannot reach!
Vertical Transmission
Thru placenta or birth!
Germline: endogenous retroviruses ~ 1 to 5% of
Location of Infection
Age and susceptibility
Sindbis virus is a lot more powerful for young mice over adults and elders.
