Evolution of Infectious Disease
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110 Terms
What are the mathematical models of virus dynamics?
The model is used to predict the number of virus-infected cells and target cells over time
What is ODEs?
equation describes the rate of change over small time interval
What outcomes are possible in the ODE model?
failure to establish infection and successfulness establishment of infection
What is the equilibrium/steady state?
rate of change of population is 0, or the population stays constant over time
What is the basic reproductive ratio of the virus?
average number of newly infected cells produced by a single infected cell during its lifespan when it is placed in a pool of susceptible cells
What does it mean when Ro > 1?
One infected cell on average gives rise to more than one newly infected cells during its lifespan
What happens when on average Ro < 1?
one infected cells gives rise on average to less than one newly infected cell during its lifespan
What happens when Ro =1?
one infected cell gives rise on average to exactly one newly infected cell leading to the infection level to stay constant
What is the effective reproduction number?
Re, the virus reproductive potential when the infection is already wide spread
What are the three phases of the HIV virus?
acute, chronic or asymptomatic and AIDS
What is the acute phase of HIV?
rapid virus growth with or without symptoms. if symptoms occur its genera; flu like symptoms
What is the chronic/asymptomatic phase of HIV?
The levels of virus are significantly reduced, there are no symptoms and the virus levels are steady
What is the AIDS phase of HIV?
CD4 helper cell levels are significantly reduced, which leads to weakened immunity, allowing for invasion of opportunistic infections
What are the three types of variability of HIV?
typical progressor (5-10 years), rapid progressor (few months), elite controllers (20 years)
What was the leading hypothesis for the chronic phase of HIV?
the virus is latent and is then spontaneously awakened after years
this wa slater proven wrong
What do reverse transcriptase inhibitors do?
They prevent infection of new cells, but the drug does not impact cells that are already infected
however once cell is infected, virus production and virus induced cell death are inhibited by drug
Does reverse transcriptase affect the death rate of the infected cells?
the death rate is uninfected only the infection rate is changed
What is the real explanation of the chronic phase of hiv?
the virus has a fast turnover and has fast cell death and cell infection
What are the three phases of decline after giving reverse transcriptase inhibitors for HIV?
fast decline due to the death of the productively infected CD4 T cells
slower phase, death of infected macrophages, 5-10 days
slowest phase, death of latently infected cells, 100 days
Why is it not possible to eradicate HIV solely using a reverse transcriptase?
the latently infected cells are considered a viral reservoir that enable to virus to persist in the the patient during drug treatment
What are the most recent treatment goal of HIV?
the eradication of the the latently infected cells, this could lead to a cure
What is the shock and kill treatment for HIV?
The treatment now used to wake up latent CD4-infected cells and kill them
however, this is not completely effective
When are drug resistance genes likely to be generated?
before treatment since that is when the virus is able to replicate a lot
What is the fitness cost for the resistant mutants?
They replicate more slowly than sensitive viruses, thus, they are disadvantageous in the absence of treatment compared to sensitive viruses
What are the competitive exclusion principle?
if 2 species share a common resource, such as food, the superior competitor wins and excludes the inferior competitor
What is the mutation-selection balance?
average level of resistance
What does p represent?
role of CTL mediated killing of infected cells
What is the equilibrium for infected cells?
I = b/c = death rate of CTL/division of CTL
What happens when CTL has a fast death rate?
CTL has short-term memory and thus viruses persistence
What are the implications for the role of CTL memory in virus persistence?
CTL might be required to make sure that the first infection with a given virus is cleared and persistent infection is not established
What is antigenic escape?
when there is a point mutation in the epitope that prevents recognition by immune responses
What is the cat and mouse game of epitopes and immune responses?
also called evolutionary rescue, the epitopes can do antigenic escape while the immune system can mount an response to the new escape variant
What is the asymmetry that exists with HIV?
while other just have the cat and mouse game, HIV is more complex and attacks and kills the CD4 game, making it take longer for the immune response to mount an response against the newly mutated epitope
What is the diversity of the virus population in the acute phase?
since there is no selection pressure, the vial population is homogenous
What is the diversity of the virus population in the chronic phase?
there is a big selection pressure since cells are fighting over target cells leading to diversified virus population
What is the diversity of the virus population in the AIDs phase?
since there is reduced selection pressure, the viral population becomes homogenous
What is hapens when injected mice with late stage SIV?
the disease became more virulent which likely contributes to the progression to AIDs
What is immunodominance?
when there is an immune response against multiple epitopes
however only one of the CTLs usually survive and the others eventually decline
Where does HIV replicate?
in the lymphoid tissues
What is the extrafollicular compartment of the lymph nodes?
holds the CD8 cells
What is the follicular compartment of the lymph node?
where the T cells help the B cells
Why are there more virus in the follicular compartment?
because the CTLs do not reside in the follicular compartment which makes it a immune privileged site
How does coinfection of an cell take place?
when a virus first infects the cell the receptor is still kept for about a day until the receptor is downregulated, during this time a second virus can infect the cell
what is cell to cell transissions?
through the virological synapse the virus is pumped into another cell which is likely to cause co-infection
Which one contributes more the virus spread synaptic or free virus transmission?
they contribute approximately equally to virus spread through the target cells
What is LCMV?
an RNA virus that causes lymphocytic choriomeningitis in humans and mice
What are the characteristics of LCMV?
comes in different strains that differ in viral replication rate and differ in cell types they infect
virus does not kill the the cell when it replicates
only way to kill infected cell if for CTL to kill it
What are outcomes of LCMV infection?
viral clearance, controlled persistent infection, CTL induced pathology and CTL exhaustion
What is CTL-induced pathology?
when the virus persists at high levels causing chronic killing of tissue and a depletion of tissues over time leading to pathology and death
Not autoimmunity
What is CTL exhaustion?
the virus persists at high levels while the CTL goes extinct, no pathology
What are lytic CTL responses?
kills the infected cells
What are the non lytic responses?
CTL secrete factors that inhibit virus replication in the cell without killing the cell
What is a cytopathic virus?
virus that kills cells
What should be the response for slow non-cytopathic virus?
a lytic response alone is likely sufficient to clear the infection, without causing pathology
What should be the response for fast non-cytopathic virus?
a combination of lytic and non-lytic responses is needed to clear the infection effectively while minimizing tissue damage.
if only have a lytic response, this is likely to induce pathology, unless it is very strong
What should be the CTL response cytopathic virus?
lytic response alone or non-lytic response alone is sufficient, whether the virus is slow or fast replicating
What does the strength of the effector response illustrates?
how CTL response are very similar to predator-prey dynamics in ecology, since when the predators become less effective, more CTL are generated and so you have the same number of infected cells
What do viruses need to replicate?
a host cell
What are the types of infectious agents?
eukaryotic multicellular
eukaryotic unicellular
prokaryotic bacteria
What is the capsid?
proteins that protect the genetic material of viruses
What are capsomers?
the protein subunits that make up capsid
What are nucleocapsid?
the genome and the capsid
What are “naked virus particles”?
when the virus only has the genome and capsid
What are “enveloped viruses”?
when there is an envelope of the cell membrane is wrapped around the nucleocapsid
How are viruses replicated?
by geometric structure and by genetic material and hence replication mechanism
What are the steps of basic replication patterns?
absorption
entry
exposure to host metabolic machinery
expression of viral proteins and replication of the genome
assembly of new virus particles
exit of progeny virus from host cells
What are the different modes of virus exit?
lytic and budding
What is lytic exit?
when there are so many viruses in the cell that it explodes
What is budding exit?
when the virus buds off the cell membrane and keeps the cell alive
What are the 7 classes of Baltimore Classification?
dsDNA
ssDNA
dsRNA
ssRNA + sense
ssRNA, - sense
diploid ssRNA
circular dsDNA
What is the life cycle of dsDNA viruses?
replicates and transcribes the same way as regular human DNA, and then the proteins and progeny DNA come together to make the progeny virus
What is the life cycle of ssDNA viruses?
the ssDNA replicates and then becomes double stranded
then proceeds same as dsDNA viruses
What are the life cycle of dsRNA viruses?
use the RDRP to make mRNA
then makes RDRP which helps to make the independent virus
What is the life cycle of + sense ssRNA viruses?
is treated as mRNA, so can immediately uses the RNA replicative complex to replicate and make proteins (RDRP)
What is the life cycle of - sense ssRNA?
uses the RDRP brought in to be able to make mRNA
then, it makes the RDRP needed to replicate
What is life cycle of diploid ssRNA viruses?
ssRNA uses reverse transcriptase to turn into dsDNA
uses integrase to go into the viral dna
then replicates as normal
What is protease?
in the retrovirus life cycle, turns the proteins into the casing around the virus
What is the epitode?
refers to the exact sequence of the protein that is recognized by the immune cell
What is the lymphoid progenitor?
makes the dendritic, NK, T, and B cell produced by the stem cell
What are the primary organs?
bone marrow and thymus
where immune cells are produced from stem cells
What are secondary organs?
lymph nodes and spleen
where mature immune cells reside and react to infections
What are lymph nodes?
tissue fluid enters through lymphatic cappilaries
What are lymphatic vessels?
where immune cells screen for pathogens in lymph node fluid
What is the spleen?
screens blood for pathogens
How many amino acids in the variation region of the variable region?
110 amino acids
How do macrophages recognize antibodies as an opsonisin?
the Fc receptor on macrophages recognizes the antibody-antigen complex
What are complements?
complements are a collection of serum glycoproteins that can perforate cell membranes
What is c3b?
-perforate cell membranes
-enable macrophages
-red blood cells can recognize c3b-antigen complex and transport them to liver for removal
What is IgG?
most abundant
helps with opsonization, complement activation, crossing placenta
What is IgM?
5-10% of total Igs
one of the first antibodies to be produced, has an pentameric structure
What is IgA?
10-15% of total Igs
predominant class in external secretion
can form dimers
What is IgE?
very low concertation
very potent so involved in hypersensitivity reactions, binds to basophils and cells to release granules
What is IgD?
role is unknown
What is functional felxibilty?
joining of V and J can be imprecise
What is allelic exclusion?
one allele is randomly chosen and the other is silenced for b cells
T or F: In HIV infection, the number of infected cells in the follicular and extra follicular compartments in the lymphoid tissue is similar to each other?
yes, since it depends on the amount of CTL
What are spatial structures in evolutionary models?
subdivison of the population into demes or patches where they interact with only with their nearest neigighbors
How do number of mutants compare between well mixed and spatial poulations?
number of mutants more in spatial populations
What happens when a virus is treated with a drug and the R0 goes from 8 to 1.01?
It is resistant to the drug
How does the compartmental structure of the lymphoid tissue contribute to the evolution of the HIV infection?
can delay the time to escape mutant invasion for strong CTL responses