Mechanism of viral infection and pathogenesis

Question 1

Describe and explain the impact of a virus’ life cycle on the disease process

Answer 1

1) Attachment and Entry:

• Viruses first attach to a specific receptor on a host cell surface, a process mediated by a viral surface protein, highly specific and determines the type of cell (tropism) the virus can infect
• For example, HIV binds to CD4 molecules, which are found on certain immune cells, leading to immunodeficiency
• SARS-CoV-2 virus uses the spike protein to bind to the ACE2 receptor present mainly in the lung cells, leading to respiratory symptoms

2) Uncoating and Replication:

• Viral genetic material takes over the host’s cellular machinery to replicate and produce more viral proteins
• disrupt normal cell function, leading to cell damage or death

3) Transcription/Translation and Assembly:

• The viral genetic material directs the host cell to prioritise the production and assembly of new viral particles
• Certain viral proteins can also modulate the host’s immune response, thereby impacting disease progression such as down-regulating MHC molecule

4) Release:

• Newly formed viral particles are released from the host cell to infect more cells
• This can occur through budding (in enveloped viruses), where the virus acquires a part of the host cell membrane, or by cell lysis (in non-enveloped viruses), leading to cell death
• Both processes can cause inflammation and tissue damage, as budding does not immediately kill the cell. but causes cell damage over time

5) Latency and Reactivation:

• herpesviruses and HIV, can become latent, integrating their genetic material into the host’s genome and remaining dormant for varying periods
• During latency, the individual may be asymptomatic, but reactivation can occur under certain conditions (e.g., stress, immune suppression), leading to recurrent disease

6) Immune Evasion and Disease Modulation:

• Viruses have evolved strategies to evade the host’s immune response, which can significantly influence disease progression
• For instance, HIV targets and depletes CD4+ T cells, a crucial component of the immune system, leading to progressive immune suppression and AIDS
• Similarly, some viruses can suppress interferon response, a critical antiviral defense mechanism of the host

7) Viral Transformation and Oncogenesis:

• Certain viruses can induce cellular transformation, leading to uncontrolled cell growth and cancer
• Human Papilloma Virus (HPV) and Hepatitis B and C viruses are well-known for their oncogenic potential, causing cervical and liver cancers

Question 2

Describe how factors like the route of entry and tissue specificity affect the disease outcome

Answer 2

Route of Entry:

1) Respiratory Route:

• Respiratory viruses like the influenza virus, coronaviruses (such as SARS-CoV-2), and rhinovirus typically enter the body through the nasal or oral cavity, causing symptoms such as cough, sore throat, and fever
• these viruses can spread to the lungs, causing pneumonia

2) Oral Route:

• Pathogens that enter the body orally, such as Salmonella or norovirus, typically affect the gastrointestinal system, leading to symptoms such as vomiting, diarrhea, and abdominal pain

3) Sexual Route:

• Sexually transmitted infections (STIs) like HIV and herpes simplex virus enter the body through sexual contact, primarily affecting the reproductive and urinary systems

4) Skin:

• Certain pathogens, such as the rabies virus or tetanus bacteria, can enter through wounds or bites in the skin

Tissue Specificity:

1) Neuotropic Viruses:

• Viruses like poliovirus and rabies virus specifically target nerve cells, leading to neurological symptoms like paralysis or aggressive behavior

2) Hepatotrophic Viruses:

• These viruses, such as hepatitis B and C, specifically infect liver cells and can lead to liver diseases like hepatitis or cirrhosis

3) Dermotrophic Viruses:

• Viruses like varicella-zoster (causing chickenpox and shingles) and measles virus infect skin cells, leading to rashes and other skin symptoms

4) Cardiotropic Virsues:

• Viruses like Coxsackie B can specifically infect heart muscle cells, leading to conditions like myocarditis

Question 3

Discriminate between acute infections, latent infections, and chronic/persistent infections; in other words, the patterns of viral infection

Answer 3

Acute Infections:

• typically have a rapid onset and a relatively short duration
• The virus replicates quickly, and the infection usually leads to an immune response that eliminates the virus from the body, resulting in recovery
• influenza virus and the norovirus (which causes gastroenteritis)

Latent Infections:

• virus remains in a dormant state within the host cell after the acute phase of the infection has resolved
• It does not cause disease or damage to the host cell during this period but can reactivate under certain conditions to produce active disease
• The herpes simplex virus, which causes cold sores and genital herpes, is an example of a virus that can exist in a latent state
• After the primary infection, the virus can remain dormant in nerve cells and reactivate to cause recurrent episodes of disease

Chronic/Persistent Infections:

• the virus is not cleared by the immune system and remains active in the body for an extended period, potentially lifelong
• These infections can lead to ongoing symptoms and can be associated with progressive damage to tissues or organs
• Examples include the human immunodeficiency virus (HIV) and hepatitis B and C viruses, which can lead to the development of AIDS, liver cirrhosis, and liver cancer, respectively

Question 4

Discriminate between cytopathogenic and non-cytopathogenic infections or how viruses damage host tissues

Answer 4

Cytopathogenic Infections:

Virus itself causes direct harm to the host cells

1) Cell Lysis:

• The virus replicates within the host cell until the cell bursts, releasing new virions. This causes the cell to die and can lead to tissue damage

2) Cell transformation:

• Viruses can alter the normal function of a cell, leading to abnormal cell growth and potentially resulting in cancer
• HPV can lead to cervical cancer

3) Inclusion bodies:

• These are structures that some viruses form within host cells
• disrupt the normal functioning of the cell and contribute to cell death

Non-cytopathogenic Infections:

Indirect; causes immune responses to harm the host.

1) Immune-mediated cell destruction:

• The host’s immune system recognises infected cells and targets them for destruction
• Leads to tissue damage, particularly if the infection is widespread

2) Immune complexes:

• In response to a viral infection, the immune system produces antibodies
• These antibodies can bind to viral particles to form immune complexes, which can deposit in various tissues and cause inflammation and damage

3) Autoimmunity:

• immune response to a viral infection can inadvertently target the body’s own tissues, resulting in autoimmune disease

One example of a non-cytopathic virus is the Hepatitis C virus. The virus itself does not kill liver cells, but the immune response against infected liver cells leads to inflammation and potentially cirrhosis or cancer

Question 5

Describe to what extent the symptoms of infection a result of the host’s immunological response

Answer 5

1) Inflammation:

• When pathogens enter the body and breach the body’s defences, the innate immune system is activated first
• Immune cells such as macrophages and dendritic cells detect the pathogen using PRRs and respond by releasing pro-inflammatory cytokines
• These molecules serve to coordinate the immune response, but they also have local effects like increasing blood flow and permeability of blood vessels, which allows more immune cells to migrate to the site of infection
• Results in the classic signs of inflammation - redness, heat, swelling, and pain
• Lead to discomfort and tissue damage if not properly regulated

2) Fever:

• When immune cells detect a pathogen, they produce pyrogenic (fever-causing) cytokines like IL-1, IL-6, and TNF-ɑ
• These cytokines act on the hypothalamus in the brain, raising the body’s set point for temperature and inducing fever
• Fever can help to inhibit the growth of some pathogens and enhances immune cell function

3) Cell Death and Tissue Damage:

• Cytotoxic T lymphocytes and Natural Killer cells can kill host cells infected with viruses or other intracellular pathogens, resulting in tissue damage
• inflammation resulting from immune response can also harm healthy tissues
• Prolonged inflammation can lead to chronic diseases

4) Immune Complex-Mediated Damage:

• Antibodies form complexes with antigens from the pathogen
• These immune complexes can deposit in various tissues and organs, triggering inflammation and damage

5) Cytokine Storm:

• Immune response to an infection can become dysregulated, leading to the overproduction of cytokines in a phenomenon known as a cytokine storm
• This overreaction can cause severe inflammation and damage to the host’s own tissues and organs

6) Sickness Behaviour:

• includes symptoms like fatigue, decreased appetite, social withdrawal, and changes in sleep patterns
• While this behaviour is thought to be beneficial by promoting rest and recovery, it contributes to the symptoms experienced during an infection

7) Autoimmunity:

• immune response can mistakenly target the body’s own tissues, resulting in autoimmunity
• occur due to molecular mimicry, where parts of the pathogen resemble the host’s own proteins
• Alternatively, the inflammation caused by an infection can expose normally hidden self-antigens to the immune system