Viral pathogenesis

Summary

Viral 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

• 🔬 **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.
• 🌐 **Disease Summation**: Viral disease results from the combined effects of viral replication and the host's immune response against the virus.
• 🧬 **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.
• 🔄 **Pathogenesis Factors**: Key factors influencing viral pathogenesis include transmission, entry, spread, tropism, virus virulence, and host factors.
• 🌱 **Infection Cycle**: Viruses establish infections by hijacking host cells, evading immune responses, and undergoing complex interactions that may harm the host, thus demonstrating pathogenicity.
• 📍 **Transmission & Entry**: Successful viral infection requires sufficient viral quantity, accessible host cells with appropriate receptors, and ineffective or absent host defenses.
• 📈 **Dissemination & Replication**: After initial entry, viruses can cause localized or systemic infections, spreading through blood or lymphatic systems and undergoing secondary replication.
• 🔔 **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.
• 🔑 **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.
• 👤 **Host Factors**: Host genetics, age, and immunocompetence significantly affect how viral infections manifest, with some individuals being more susceptible to severe disease.
• 🛡️ **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

00:00

🦠 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.

05:02

🔬 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.

10:03

🧬 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.

15:06

🛡 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.

Keywords

💡Viral Pathogenesis

Viral pathogenesis refers to the study of how viruses cause diseases in their hosts, particularly at the cellular or molecular level. It is a specialized field within virology that focuses on the mechanisms of disease development. In the video, this term is central as it encompasses the various factors and processes by which viruses infect, replicate within, and cause harm to their hosts. The script discusses how viral replication and the host's immune response contribute to the disease outcome.

💡Virulence Factors

Virulence factors are specific characteristics of a virus that enable it to cause disease. These factors can include the ability to enter host cells, evade the immune system, and cause damage to the host. In the context of the video, virulence factors are mentioned as essential for a virus to establish infection and overcome the host's defenses, with examples such as the ability of a virus to hijack host factors for replication.

💡Host Defenses

Host defenses are the body's natural mechanisms to fight off infections, including physical barriers like skin and mucous membranes, as well as immune responses. The video script highlights how viruses must overcome these defenses to establish an infection, and how individual differences in these defenses can affect the severity of the disease.

💡Tropism

Tropism in viral pathogenesis refers to the preference of a virus to infect specific types of cells or tissues. This is determined by the ability of viral surface proteins to bind to receptors on target cells. The script explains how tropism influences the pathogenesis by determining which cells the virus can infect, which in turn affects the disease's manifestation, as seen with HIV's switch in co-receptor usage.

💡Viral Replication

Viral replication is the process by which a virus duplicates itself within a host cell. It is a critical step in the viral life cycle and a key aspect of pathogenesis. The video discusses how viruses must hijack host cell machinery for replication and how this process can lead to cellular damage and disease.

💡Innate Immune Response

The innate immune response is the body's first line of defense against infections, including viral infections. It involves immediate reactions to pathogens without the need for prior exposure. The script mentions how viruses must modulate the host's innate immune response to facilitate their replication and avoid elimination by the host's immune system.

💡Dissemination

Dissemination is the spread of a virus from the initial site of infection to other parts of the body. This can occur through the blood, lymphatic system, or other means. The video script describes how dissemination allows the virus to infect secondary tissues and target organs, which is a significant aspect of systemic viral diseases.

💡Shedding

Shedding refers to the release of virus particles from an infected individual into the environment, which can then lead to transmission to other hosts. The video discusses how viruses spread to sites where shedding can occur, such as the respiratory and genital tracts, facilitating the spread of the virus to new hosts.

💡Cytopathic Effects

Cytopathic effects are the changes in host cells caused by viral infections, which can lead to cell damage or death. The video script explains how viruses can induce cytopathic effects through various mechanisms, such as releasing enzymes that degrade cellular components or inhibiting cellular functions, contributing to the disease process.

💡Immunopathology

Immunopathology refers to the tissue damage caused by the host's immune response to an infection. The video script mentions how the host's immune response can sometimes cause more harm than the virus itself, leading to severe pathological consequences, such as cytokine storms or autoimmune responses.

💡Incubation Period

The incubation period is the time between exposure to a virus and the appearance of symptoms. The video script discusses how the length of the incubation period can vary depending on factors such as the virus's mode of entry and the host's immune response, and how it influences the progression and detection of the disease.

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