Viral pathogenesis
Summary
TLDRViral pathogenesis is the study of how viruses cause disease in hosts at the cellular or molecular level. It involves understanding the complex interactions between the virus and the host's immune system, including viral transmission, entry, replication, and the host's defense mechanisms. Key factors influencing pathogenesis include virus tropism, virulence, and host factors such as genetics and immune status. The video script delves into the life cycle of viruses, the role of viral and host factors in disease development, and the mechanisms by which viruses cause damage, including direct cytopathic effects and immune-mediated damage.
Takeaways
- đŹ **Viral Pathogenesis Definition**: It's the study of how viruses cause diseases in hosts at the cellular or molecular level, focusing on the mechanisms of disease initiation and progression.
- đ **Disease Summation**: Viral disease results from the combined effects of viral replication and the host's immune response against the virus.
- 𧏠**Virulence Factors**: Viruses use specific virulence factors to initiate infection and replicate throughout the body, overcoming host inhibitory effects like physical barriers and immune defenses.
- đ **Pathogenesis Factors**: Key factors influencing viral pathogenesis include transmission, entry, spread, tropism, virus virulence, and host factors.
- đ± **Infection Cycle**: Viruses establish infections by hijacking host cells, evading immune responses, and undergoing complex interactions that may harm the host, thus demonstrating pathogenicity.
- đ **Transmission & Entry**: Successful viral infection requires sufficient viral quantity, accessible host cells with appropriate receptors, and ineffective or absent host defenses.
- đ **Dissemination & Replication**: After initial entry, viruses can cause localized or systemic infections, spreading through blood or lymphatic systems and undergoing secondary replication.
- đ **Shedding & Transmission**: Viruses spread to sites where they can be shed into the environment, such as respiratory and genitourinary tracts, facilitating transmission to new hosts.
- đ **Tropism & Virus Factors**: Tropism, determined by viral surface protein-receptor interactions, dictates the virus's preferred replication site and influences pathogenicity. Viral genetics play a role in determining virulence and pathogenesis.
- đ€ **Host Factors**: Host genetics, age, and immunocompetence significantly affect how viral infections manifest, with some individuals being more susceptible to severe disease.
- đĄïž **Disease Mechanisms**: Viral infections can cause disease through direct cytopathic effects, immune system-mediated damage, or by inducing autoimmune responses.
Q & A
What is viral pathogenesis?
-Viral pathogenesis is the study of the processes and mechanisms by which viruses cause diseases in their target hosts, often at the cellular or molecular level. It is a specialized field of virology that focuses on the qualitative description of how an initial infection leads to disease.
How does viral replication contribute to disease?
-Viral replication contributes to disease by causing the sum of effects on the host and the host's subsequent immune response against the virus. The process of viral replication can disrupt normal cellular functions and lead to cell death or tissue damage.
What are the factors that affect pathogenesis?
-Factors affecting pathogenesis include transmission, entry and spread within the host, tropism, virus virulence and disease mechanisms, and host factors in host defense.
What is meant by viral tropism?
-Viral tropism refers to the virus's preferential site of replication in discrete cell types within an organ. It is determined by the ability of viral surface proteins to bind to specific surface receptors of target cells.
How do viruses establish infections in host cells?
-Viruses establish infections in host cells by hijacking host factors and evading the host immune response for efficient replication. This often requires complex interactions between the virus and host factors.
What are the important steps in a virus life cycle that shape pathogenesis?
-Important steps in a virus life cycle that shape pathogenesis include transmission from a host to another, entry of the virus into the body, local replication, dissemination and spread to secondary tissues, secondary replication, and shedding of the virus into the environment for onward transmission.
How do viruses overcome inhibitory effects present in the host?
-Viruses overcome inhibitory effects in the host by using specific virulence factors and by modulating the host's innate immune response to prevent elimination while facilitating its replication.
What is the role of viral genetics in determining the degree of viral pathogenesis?
-Viral genetics encoding viral factors determines the degree of viral pathogenesis, or virulence. Different virus strains with different virus factors can lead to different degrees of virulence, which affects the severity of disease.
How do host factors influence viral pathogenesis?
-Host factors such as genetic factors, age, and immunocompetence play a significant role in determining the outcome of a viral infection. These factors can influence whether the host can effectively modulate the infection and mount an immune response.
What are the different mechanisms by which viral infections cause disease?
-Viral infections can cause disease through direct cytopathic effects, inducing cell death via apoptosis, transforming host cells into cancer cells, and causing immunopathology due to the host's immune response. Additionally, some viruses can trigger autoimmune responses.
How does the incubation period of a virus affect its pathogenesis?
-The incubation period, which is the time taken for the onset of disease after first contact with the virus, can vary depending on factors such as the distance the virus travels to the target organ and the host's immune response. A longer incubation period may allow the virus more time to replicate before symptoms appear.
Outlines
đŠ Viral Pathogenesis Overview
Viral pathogenesis is a specialized field in virology that investigates how viruses cause diseases in their hosts at the cellular or molecular level. It encompasses the process by which an initial infection leads to disease, including viral replication and the host's immune response. Key factors influencing pathogenesis are transmission, entry, spread within the host, tropism, virus virulence, and host factors. The life cycle of a virus involves transmission, entry, local replication, dissemination, secondary replication, and shedding, which are essential for understanding how viruses establish infections and evade host defenses.
đŹ Dissemination and Transmission Factors
This paragraph delves into the mechanisms of viral dissemination and transmission. It explains how viruses spread to sites where they can be shed into the environment, such as respiratory and urogenital tracts, facilitating transmission to new hosts. Factors affecting pathogenesis include virus tropism, virus factors, and host factors. Tropism is determined by the virus's ability to bind to specific host cell receptors, which dictates the virus's preferred site of replication and can lead to the destruction of particular cell populations. The accessibility of host tissues to the virus and the virus's genetic makeup also play crucial roles in pathogenesis.
𧏠Host and Virus Factors in Pathogenesis
The third paragraph focuses on the interplay between host and virus factors in viral pathogenesis. Host factors such as genetics, age, and immunocompetence can significantly influence the outcome of a viral infection. Virus factors, including viral genetics and the encoding of specific viral proteins, determine the degree of virulence and the virus's ability to overcome host defenses. The paragraph also discusses how viruses can manipulate the host immune response through various strategies, such as encoding decoy receptors or homologs of host cytokines, to enhance their pathogenicity.
đĄ Disease Mechanisms and Immune Response
This section explores how viral infections lead to disease through direct cytopathic effects, induction of apoptosis, and transformation of host cells into cancer cells. It also examines the role of the host immune system in mediating disease, including immunopathology caused by an excessive immune response and the potential for autoimmune responses triggered by viral infections. The paragraph concludes with a discussion on the incubation period of viruses and the evolution of virulence, highlighting how viruses and hosts can influence each other's evolution over time.
Mindmap
Keywords
đĄViral Pathogenesis
đĄVirulence Factors
đĄHost Defenses
đĄTropism
đĄViral Replication
đĄInnate Immune Response
đĄDissemination
đĄShedding
đĄCytopathic Effects
đĄImmunopathology
đĄIncubation Period
Highlights
Viral pathogenesis is the study of how viruses cause diseases in their hosts at the cellular or molecular level.
Pathogenesis involves the qualitative description of how an initial infection leads to disease.
Viral disease results from the sum of effects of viral replication and the host's immune response.
Viruses initiate infection throughout the body due to specific virulence factors.
Inhibitory effects such as distance, physical barriers, and host defenses affect viral pathogenesis.
Viral pathogenesis is influenced by transmission, entry, spread, and host factors.
Viruses must hijack host factors and evade the immune response for efficient replication.
Important steps in the virus life cycle include transmission, entry, replication, dissemination, and shedding.
For successful infection, a sufficient quantity of virus, accessible cells, and ineffective host defenses are required.
Viruses often enter through the mouth, nose, genital tract, or damaged skin.
Local replication and spread involve the virus hijacking the host cell machinery and modulating the immune response.
Dissemination and secondary replication can occur through the blood or lymphatic system.
Shedding and secondary transmission involve the virus spreading to sites where it can be transmitted to another host.
Virus tropism, determined by viral surface proteins, dictates the preferential site of replication.
Viral genetics encoding viral factors determines the degree of viral pathogenesis or virulence.
Host factors such as genetics, age, and immunocompetence play a role in viral pathogenesis.
Viral infections can cause disease through direct cytopathic effects, immune evasion, and immunopathology.
Incubation periods vary among viruses and are influenced by factors such as virus traversal and host immunity.
The evolution of virulence can be observed in emerging viruses and their hosts over time.
Transcripts
viral pathogenesis viral pathogenesis
is the study of the process and
mechanisms by which viruses
cause diseases in their target hosts
often
at the cellular or molecular level it is
a specialized field of study in virology
pathogenesis is a qualitative
description of the process
by which an initial infection causes
disease
viral disease is the sum of the effects
of viral replication
on the host and the host's subsequent
immune response against the virus
viruses are able to initiate infection
dispersed throughout the body
and replicate due to specific virulence
factors
there are several factors that affect
pathogenesis
some of these factors include virulence
characteristics of the virus that is
infecting
in order to cause disease the virus must
also
overcome several inhibitory effects
present in the host
some of the inhibitory effects include
distance
physical barriers and host defenses
these inhibitory effects may differ
among individuals due to the inhibitory
effects being genetically controlled
viral pathogenesis
is affected by various factors one
transmission
entry and spread within the host two
tropism
three virus virulence and disease
mechanisms
four host factors in host defense
mechanisms of infection viruses need to
establish infections in host cells
in order to multiply for infections to
occur
the virus has to hijack host factors and
evade the host immune response for
efficient replication
viral replication frequently requires
complex interactions
between the virus and host factors that
may result in deleterious effects in the
host which confers the virus its
pathogenicity
important steps of a virus life cycle
that shape pathogenesis
transmission from a host with an
infection to a second host
entry of the virus into the body local
replication
in susceptible cells dissemination and
spread to secondary tissues
and target organs secondary replication
in susceptible cells shedding of the
virus into the environment
onward transmission to third host
primary transmission three requirements
must be satisfied
to ensure successful infection of a host
firstly there must be sufficient
quantity of virus available to initiate
infection cells at the site of infection
must be accessible
in that their cell membranes display
host encoded receptors
that the virus can exploit for entry
into the cell
and the host anti-viral defense systems
must be ineffective or
absent entry to host
viruses causing disease in humans often
enter through the mouth nose genital
tract or through damaged areas of skin
so cells of the respiratory
gastrointestinal
skin and genital tissues are often the
primary site of infection
some viruses are capable of transmission
to a mammalian fetus
through infected germ cells at the time
of fertilization
later in pregnancy by the placenta and
by infection at birth
local replication and spread following
initial
entry to the host the virus hijacks the
host cell machinery to undergo viral
amplification
here the virus must modulate the host
innate immune response
to prevent its elimination by the body
while facilitating its replication
replicated virus from the initially
infected cell then dispersed to infect
neighboring susceptible cells possibly
with spread to different cell types like
leukocytes
this results in a localized infection in
which the virus mainly spreads and
infects adjacent cells to the site of
entry
otherwise the virus can be released into
extracellular fluids
examples of localized infections include
common cold rhinovirus flu paren
influenza
gastrointestinal infections rotavirus or
skin infections papillomavirus
dissemination and secondary replication
in other cases the virus can cause
systemic disease through a disseminated
infection spread throughout the body
the predominant mode of viral
dissemination occurs through the blood
or lymphatic system
some of which include viruses
responsible for chickenpox
varicella zoster virus smallpox variola
hiv human immunodeficiency virus
a minority of viruses can disseminate
via the nervous system
notably the poliovirus can be
transmitted via the fecal oral route
where it initially replicates in its
site of entry
the small intestine and spread to
regional lymph nodes
then the virus disseminates via the
bloodstream
into different organs in the body eeg
liver
spleen followed by a secondary round of
replication
and dissemination into the central
nervous system to damage motor neurons
shedding and secondary transmission
finally the viruses spread to sites
where shedding into the environment
can occur the respiratory alignmentary
and eurogenital tracts and the blood are
the most frequent sites of shedding in
the form of bodily fluids
aerosols skin excrement the virus would
then go on to be transmitted to another
person
and establish the infection cycle all
over again
factors affecting pathogenesis
there are a few main overarching factors
affecting viral diseases
virus tropism virus factors
factors host factors
basis of virus tropism virus tropism
refers to the virus preferential site of
replication
in discrete cell types within an organ
in most cases
tropism is determined by the ability of
the viral surface proteins to fuse
or bind to surface receptors of specific
target cells
to establish infection thus the binding
specificity of viral surface proteins
dictates tropism
as well as the destruction of particular
cell populations
and is therefore a major determinant of
virus pathogenesis
however co-receptors are sometimes
required in addition to the binding of
cellular receptors
on host cells to viral proteins in order
to establish infection
for instance hiv-minus-1 requires target
cells to express co-receptors
ccr5 or cxcr4
on top of the cd4 receptor for
productive viral attachment
interestingly hiv minus one can undergo
a tropism switch
where the virus glycoprotein gpo120
initially uses
ccr5 mainly on macrophages as the
primary co-receptor
for entering the host cell subsequently
hiv minus one switches to bind to cxcr4
mainly on t
cells as the infection progresses in
doing so transitions the viral
pathogenicity to a different stage
apart from cellular receptors viral
tropism
can also govern by other intracellular
factors
such as tissue specific transcription
factors
an example would be the jc polyamovirus
in which its tropism is limited to glial
cells since its enhancer is only active
in glial cells
and jc viral gene expression requires
host
transcription factors expressed
exclusively in glial cells
the accessibility of host tissues and
organs to the virus also regulates
tropism
accessibility is affected by physical
barriers
such as in enteroviruses which replicate
in the intestine since they are able to
withstand bile digestive enzymes and
acidic environments
virus factors factors
viral genetics encoding viral factors
will determine the degree of viral
pathogenesis
this can be measured as virulence which
can be used to compare the quantitative
degree of pathology between related
viruses
in other words different virus strains
possessing different virus factors can
lead to different degrees of virulence
which in turn can be exploited to study
the differences in pathogenesis of viral
variants with different virulence
virus factors are largely influenced by
viral
genetics which is the virulence
determinant of structural
or non-structural proteins and
non-coding sequences
for a virus to successfully infect and
cause disease in the host
it has to encode specific virus factors
in its genome to overcome the preventive
effects of physical barriers
and modulate host inhibition of virus
replication
in the case of poliovirus all vaccine
strains found
in the oral polio vaccine contain
attenuating point mutations in the five
untranslated region five utr conversely
the virulent strain responsible for
causing polio disease does not contain
these five utr point mutations
and thus display greater viral
pathogenicity in hosts
virus factors encoded in the genome
often control the tropism
routes of virus entry shedding and
transmission
in polio viruses the attenuating point
mutations are thought
to induce a replication and translation
defect to reduce the virus ability of
cross-linking to host cells
and replicate within the nervous system
viruses have also developed a variety of
immunomodulation mechanisms to subvert
the host
immune response this tend to feature
virus-encoded decoy
receptors that target cytokines and
chemokines produced as part of the host
immune response
or homologs of host cytokines as such
viruses capable of manipulating the host
cell response to infection
as an immune evasion strategy exhibit
greater pathogenicity
host factors viral pathogenesis
is also largely dependent on host
factors
several viral infections have displayed
a variety of effects
ranging from asymptomatic to symptomatic
or even critical
infection solely based of differing host
factors alone
in particular genetic factors age and
immunocompetence play an important role
is dictating whether the viral infection
can be modulated by the host mice that
possess
functional mx genes encode an enzyme
protein which can selectively inhibit
influenza replication therefore mice
carrying a non-functional mx allele fail
to synthesize the mx protein
and are more susceptible to influenza
infection
alternatively immunocompromised
individuals due to existing
illnesses may have a defective immune
system which makes them more vulnerable
to damage by the virus
furthermore a number of viruses display
variable pathogenicity depending on the
age of the host
mumps polio and epstein-barr virus cause
more severe disease in adults
while others like rotavirus cause more
severe infection in infants
it is therefore hypothesized that the
host immune system
and defense mechanisms might differ with
age
disease mechanisms how do viral
infections cause disease
a viral infection does not always cause
disease
a viral infection simply involves viral
replication in the host
but disease is the damage caused by
viral multiplication
an individual who has a viral infection
but does not display diseased
symptoms is known as a carrier damage
caused by the virus
once inside host cells viruses can
destroy
cells through a variety of mechanisms
viruses often
induce direct cytopathic effects to
disrupt cellular functions
this could be through releasing enzymes
to degrade host metabolic precursors
or releasing proteins that inhibit the
synthesis of important host factors
proteins dna and slash or rna
namely viral proteins of herpes simplex
virus can degrade host dna and inhibit
host cell dna replication
and mrna transcription poliovirus can
inactivate proteins involved in hostim
rna translation
without affecting poliovirus and rna
translation
in some cases expression of viral fusion
proteins on the surface of the host
cells
can cause host cell fusion to form
multinucleated cells
notable examples include measles virus
hiv
respiratory syncytial virus importantly
viral infections can differ by the
lifestyle strategy
persistent infections happen when cells
continue to survive despite a viral
infection and can be further classified
into latent only the viral genome is
present there is no replication
occurring and chronic basal levels of
viral replication without stimulating an
immune response
in acute infections lytic viruses are
shed at high titters
for rapid infection to a secondary
tissue slash host
whereas persistent viruses undergo
shedding at lower titters for a longer
duration of transmission months to years
lytic viruses are capable of destroying
host cells by incurring in slash or
interfering with the specialized
functions of host cells
an example would be the triggering of
necrosis in host cells infected with the
virus
otherwise signatures of viral infection
like the binding of
hiv to co-receptors ccr5 or cxcr4
can also trigger cell death via
apoptosis through host
signaling cascades by immune cells
however
many viruses encode proteins that can
modulate apoptosis depending on whether
the infection
is acute or persistent induction of
apoptosis
such as through interaction with
caspases will promote viral
shedding for lytic viruses to facilitate
transmission
while viral inhibition of apoptosis
could prolong the production of virus in
cells
or allow the virus to remain hidden from
the immune system in chronic persistent
infections nevertheless induction of
apoptosis in major
immune cells or antigen presenting cells
may also
act as a mechanism of immunosuppression
in persistent infections like hiv
the primary cause of immunosuppression
in hiv patients is due to the depletion
of cd4 plus t helper
cells interestingly adenovirus has an
eona protein to induce apoptosis by
initiating the cell cycle
and an eonb protein to block the
apoptotic pathway through inhibition of
caspase interaction
persistent viruses can sometimes
transform host cells into cancer cells
viruses such as the human papillomavirus
hpv
human t lymphotropic virus htlv etc
can stimulate growth of tumors in
infected hosts
either by disrupting tumor suppressor
gene
expression hpv or upregulating
proto-oncogene
expression hdlv damage caused by host
immune system
sometimes instead of cell death or
cellular dysfunction caused by the virus
the host immune response can mediate
disease and excessive inflammation
the stimulation of the innate and
adaptive immune system in response to
viral
infections destroys infected cells which
may lead to severe pathological
consequences to the host
this damage caused by the immune system
is known as virus-induced
immunopathology
specifically immunopathology is caused
by the excessive release of antibodies
interference and pro-inflammatory
cytokines activation of the complement
system or hyperactivity of cytotoxic
cells suppression of interference and
other cytokines can trigger cell damage
fever and flu-like symptoms in severe
cases
of certain viral infections as in avian
h5 nun
influenzae in 2005 a barren
induction of the host immune response
can elicit a flaring release of
cytokines known as a cytokine storm
in some instances viral infection can
initiate
an autoimmune response which occurs via
different proposed mechanisms
molecular mimicry and bystander
mechanism
molecular mimicry refers to an overlap
in structural similarity between a viral
antigen
and self antigen the bystander mechanism
hypothesizes the initiation of a
non-specific
and overreactive antiviral response that
tackles
self-antigens in the process damage
caused by the host itself
due to autoimmunity was observed in the
west nile virus
incubation period viruses display
variable incubation periods upon virus
entry into the host
the incubation period refers to the time
taken for the onset of disease after
first contact with the virus
in rabbi's virus the incubation period
varies with the distance traversed by
the virus to the target organ
but in most viruses the length of
incubation depends on many factors
surprisingly generalized infections by
tagaviruses have a short incubation
period due to the direct
entry of the virus into target cells
through insect bites
there are several other factors that
affect the incubation period
the mechanisms behind long incubation
periods
months or years for example are not
completely understood yet
evolution of virulence some relatively
average viruses and their natural hosts
show increased virulence upon transfer
when an emerging virus first invades a
new host species
the hosts have little or no immunity
against the virus and often suffer high
mortality
over time a decrease in virulence in the
predominant strain can sometimes be
observed
a successful pathogen needs to spread to
at least one other host
and lower virulence can result in higher
transmission rates
under some circumstances likewise
genetic resistance against the virus can
develop in a host population
over time an example of the evolution of
virulence in emerging virus is the case
of microsomatosis
in rabbits the release of wild european
rabbits in 1859
into victoria australia for sport
resulted in a rabbit plague
in order to curb with rabbit
overpopulation mixoma virus
a lethal species-specific pox virus
responsible for mycomatosis in rabbits
was deliberately released in south
australia in 1950
this led to a 90 percent decrease in
rabbit populations
and the disease became endemic in a span
of five years
significantly severely attenuated
strains of the mixoma virus were
detected
in merely two years of its release and
genetic resistance
in rabbits emerged within seven years
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