Lecture 2: Pathogenesis of Viral Material Flashcards
Pathogenesis:
Pathogenesis is the process by which a disease develops or originates in an individual.
It refers to the sequence of events and mechanisms that lead to the development and progression of a disease from its initial cause or trigger, such as an infection, genetic mutation, environmental factor, or other underlying conditions.
RNA Viruses
Review
RNA viruses are a type of viruses that use RNA (ribonucleic acid) as their genetic material.
Unlike DNA viruses, they need to encode or bring their own RNA-dependent RNA polymerase, an enzyme that’s essential for copying their RNA.
These viruses replicate their genetic material and produce new virus particles in the cell’s cytoplasm, which is outside the cell’s nucleus.
RNA viruses are known for having faster mutation rates compared to DNA viruses, which can make them more adaptable and sometimes harder to treat with vaccines or drugs.
Examples of RNA viruses include the flu virus, HIV, and the common cold virus.
DNA viruses Review
DNA viruses are a type of viruses that have genetic material made of DNA. When they infect a cell, they tend to stick around for a long time, causing what’s called a persistent infection. Most DNA viruses like to work inside the cell’s control center, which is the nucleus, to copy their DNA and reproduce.
These viruses are also smart in the way they turn their genes on and off at specific times to make more viruses without being noticed by the cell’s defenses.
Common examples of DNA viruses include herpes and chickenpox viruses.
Virulence Factors
Things viruses do to make themselves more harmful, like attaching to cells, spreading, and hiding from the body’s defenses.
Essentially, virulence factors help the virus become more effective at causing disease and spreading to new hosts.
Attenuated virus
Weakened versions of viruses with their harmful traits removed, used to make vaccines.
Acquisition
Acquisition often relates to the initial exposure to a pathogen or the process by which a microorganism or virus enters the body, which is a critical step in the development of an infection.
Initiate primary site infection
The beginning or starting of an infection at the initial or primary location in the body where a pathogen enters and establishes itself.
In many cases, the primary site of infection occurs through either the mouth (oral) or the respiratory system, where pathogens are commonly introduced into the body.
How does the body react?
Innate immune reponse will be activated, phagocytes and interferon response
Incubation Period
The time between exposure to a pathogen or disease and the appearance of the first symptoms, during which the pathogen is replicating and the individual is not yet symptomatic.
EX: Testing positive for COVID with no symptoms happens during the incubation period
Secondary Site
Only happens in some cases.
Replication happens at this second site & the adaptive immune response is triggered.
Sometimes, the adaptive immune system is able to clear out the infection.
Other times, this can develop into immunopathology, where the immune system’s activity causes harm to the host’s own tissues and results in symptoms or disease.
How can a viral infection cause immunopathology?
In some cases, the immune system may overreact to a virus, causing excessive inflammation and damage to healthy tissues.
This is often seen in diseases like COVID-19, where a hyperactive immune response can lead to severe lung damage.
& Some viruses trigger autoimmune reactions, where the immune system mistakenly attacks the body’s own cells
Resolution of a virus
After an infection, the outcome can be one of two possibilities: resolution, where the infection is successfully cleared by the immune system, or…
Persistence of a virus
or persistence, where the pathogen remains in the body and the infection continues over time.
HIV initially targets immune response cells and then can target and replicate in lymph nodes. What is this an example of?
Spread to secondary site
Asymptomatic
When an individual is infected but shows no symptoms. In some cases, the infection can even progress to secondary sites in the body without noticeable symptoms.
Prodrome
The initial phase of an illness marked by early, non-specific symptoms such as fever, aches, and chills that precede the characteristic symptoms of the disease.
What is causing the symptoms of prodrome?
Infection:
The presence of a virus, bacteria, or other pathogens in the body can stimulate the immune system and lead to symptoms like fever, aches, and chills.
Immune Response
The body’s defense mechanism against infections. Innate immunity can often resolve infections, but if not, it triggers adaptive immune responses, involving antibodies and specific immune cells.
Convalescence
The period following an illness when symptoms are improving due to tissue repair mechanisms. During this time, the body also develops immunological memory, which provides protection against future infections.
Day 1 of infection:
Acquisition Stage: This is the initial phase where the virus enters the body. It involves the exposure to the pathogen and its entry into the host. The acquisition stage is when the virus gains access to the body.
Disease Course: After the virus gets in, you might start feeling early symptoms like fever, tiredness, and mild aches. This phase happens before you get the full-blown symptoms of the illness.
Day 2 of infection
The virus continues to replicate at the primary site.
Some immune cells arrive at the site of infection.
Host response: The innate immune response intensifies.
Disease course: Still no specific symptoms, but the virus is spreading within the primary site.
Day 3 of infection:
localized inflammation at the primary site.
Immune cells work to contain the infection.
Virus replication continues.
Host response: Innate immunity remains active.
Disease course: Non-specific prodromal symptoms may appear, like mild fever and fatigue.
Day 4 of infection:
The virus continues to replicate at the primary site.
Some viral particles may spread to secondary sites.
Immune response: Adaptive immune responses, involving antibodies and specific immune cells, begin to develop.
Disease course: Prodromal symptoms, such as fever and muscle aches, may intensify. The virus may spread to other tissues.
Day 5: Spread to Secondary Sites:
Virus particles may spread to secondary sites, affecting different tissues.
The adaptive immune response becomes more targeted.
Host response: Adaptive immune responses are in full swing.
Disease course: Specific symptoms related to the affected tissues may become noticeable.
Day 6: Target Tissues affected
Virus replication and immune response are active in various tissues.
Immune cells are actively fighting the infection.
Host response: Adaptive immunity is strong.
Disease course: Specific symptoms may intensify or begin to subside, depending on the overall balance between virus replication and the immune response.
Day 7 and Beyond - Resolution or Persistence:
The disease can follow one of two paths: resolution (where the immune system successfully clears the infection) or persistence (where the virus continues to reside in the body).
Convalescence: After the infection is resolved, symptoms may persist due to tissue repair mechanisms. Immunological memory develops to provide protection against future infections.
Modes of Viral Transmission
What is the most common route of entry for viruses?
Inhalation
Inhalation
Infects oral and respiratory mucosa
The specific cells in your mouth and respiratory tract, called epithelial cells, have the right receptors that the virus can latch onto to enter and infect them.
The virus carries the tools it needs to make copies of itself once it’s inside these cells, allowing it to multiply and cause infection
Gastrointestinal
Virus sheds in feces
The virus is found in the stool, and it can be transmitted to others through contaminated food, water, or surfaces. This is often referred to as the “fecal-oral” route of transmission.
What cells in the gastrointestinal tract can help the virus spread and transport throughout the body?
M cells in Peyer’s patches
How do M cells assist with viral transmission?
M cells have a unique ability to capture viruses, bacteria, and other particles from the gut lumen. They have a specialized structure that allows them to sample the contents of the gut.
Once M cells capture viruses, they transfer these captured particles to immune cells located in the underlying lymphoid tissue.
What kind of virus would be more likely to be shed in the feces: naked or enveloped?
Naked viruses are more likely to be shed in the feces compared to enveloped viruses.
Enveloped viruses are surrounded by a lipid membrane (envelope) that is typically derived from the host cell’s membrane. This envelope is sensitive to environmental conditions and can be easily damaged by the harsh conditions in the gastrointestinal tract, such as stomach acid and digestive enzymes.
Sexual Transmission
Infections can be transmitted through sexual contact, such as during sexual intercourse, oral sex, or through contact with genital fluids.
Blood
Infections can be spread through contact with contaminated blood. This can occur through sharing needles (as seen in intravenous drug use), blood transfusions with infected blood, or contact with open wounds.
Transcutaneous
Infections can enter the body through breaks or cuts in the skin. This can happen when, for example, a person is injured, and infectious agents gain entry through the injured skin.
Maternal (fetal/neonatal)
Infections can be transmitted from a pregnant person to the developing fetus during pregnancy or to the newborn during childbirth or breastfeeding. This is often referred to as mother-to-child transmission.
Various mechanisms of dissemination from 1° site
This refers to the different ways a virus can spread from its primary (initial) site of infection to other parts of the body.
Viruses have various strategies to move from the primary site to secondary sites and cause infection at those locations.
Local spread:
This term describes the virus’s ability to move and infect nearby tissues or cells at or near the primary site of infection. Local spread is one of the initial steps in the virus’s dissemination within the body.
Viremia – in the bloodstream:
Viremia means the presence of viruses in the bloodstream. It occurs when viruses have entered the bloodstream and can be carried throughout the body, potentially infecting various organs and tissues.
infected leukocytes & lymphocytes:
Some viruses can infect white blood cells (leukocytes) and lymphocytes, which are important components of the immune system. When viruses are present in these immune cells, they can be carried through the bloodstream to other parts of the body, allowing the virus to spread.
M cells:
M cells are specialized cells found in the mucosal lining of the intestines, particularly in areas like Peyer’s patches. They play a role in capturing and transporting viruses and other particles from the gut lumen to immune cells in the gut-associated lymphoid tissue.
Transmission into the CNS:
This refers to the ability of viruses to enter the central nervous system (CNS), which includes the brain and spinal cord. Not all viruses can readily enter the CNS, but some have specific mechanisms that allow them to do so.
How can viruses reach the CNS?
Viruses can reach the cerebrospinal fluid (CSF) or the protective meninges around the brain and spinal cord through viremia (presence in the bloodstream), migration by immune cells like macrophages, or transmission from infected peripheral nervous system (PNS) neurons.
How does macrophage migration lead to the infection of the CNS?
Once macrophages have captured viruses, they can transport these viruses within their own cellular structures. This provides a means for viruses to be carried throughout the body, including to the central nervous system (CNS).
What cell type is this similar to?
Both macrophages and M cells are involved in immune responses and can transport viruses, BUT they operate in different contexts and have distinct roles.
How does a rabies virus infect the CNS? (from start to finish)
Peripheral Infection: Rabies virus usually enters the body through the bite of an infected animal, such as a rabid dog or bat. The virus initially infects peripheral tissues near the site of the bite.
Nerve Invasion: The virus has a high affinity for nerve cells (neurons). It binds to nerve endings in the peripheral tissues and then travels along the nerves in a retrograde manner, moving toward the spinal cord and brain. This retrograde transport occurs within the axons of neurons.
CNS Entry: Once the virus reaches the CNS, it can spread throughout the central nervous system, infecting various parts of the brain and spinal cord. This is when clinical symptoms of rabies typically appear.
Abortive:
An infection that fails to establish and reproduce within the host.
Inapparent
Refers to an infection that is asymptomatic, causing no noticeable consequences.
it is INAPPARENT in the body
Ex: Epstein-Barr virus (EBV)
Lytic
An infection where the virus kills the host cell during the replicative cycle.
Ex: The lytic infection of the influenza virus, where it damages and lyses host respiratory epithelial cells.
Non-lytic (Persistent)
An infection in which the host cell is not killed, and the virus does not result in cell death.
The non-lytic, persistent infection of Hepatitis B virus (HBV) in hepatocytes, which can lead to chronic hepatitis.
What are some advantages of being a lytic virus
Lytic viruses can replicate quickly, producing a large number of viral particles. This can help the virus spread within the host population.
When the host cell is lysed (ruptured), it releases numerous viral particles, which can then infect neighboring cells or be transmitted to new hosts, promoting the virus’s spread.
What are some disadvantages of being a lytic virus
Lytic infections may lead to the death of the host cell. This can be a disadvantage if the virus relies on the host cell for a prolonged period.
Immune Response: The destruction of host cells during lytic infections can trigger a strong immune response, making it more challenging for the virus to evade the host’s defenses.
Chronic
A type of non-lytic, productive infection that persists over an extended period.
Ex: HIV
Latent
A non-productive infection in which the virus remains dormant within the host cell, without active replication.
Example: Herpes Simplex Virus (HSV) can establish a latent infection in nerve cells, causing recurrent cold sores.
Recurrent
An infection characterized by on-and-off production of viral particles.
Example: Recurrent infections of Varicella-Zoster Virus (VZV) can lead to shingles outbreaks in individuals previously infected with chickenpox.
Initial Infection: The virus infects the host and may cause symptoms or an initial outbreak.
Latent Phase: After the initial infection, the virus may enter a dormant or latent state, where it remains hidden within host cells and does not actively replicate or produce symptoms.
Reactivation: At a later time, the virus may reactivate due to certain triggers, such as stress, illness, or other factors. When reactivation occurs, the virus starts replicating and can lead to the recurrence of symptoms or outbreaks.
