Week 24 - Viral infections, oncoviruses & antiviral chemotherapy Flashcards
Dynamics of viral infections
Viral pathogenesis
->Process for a virus producing a disease
-Infect their specific host’s cells
-Replicate efficiently within the host
-Damage targeted tissues
-Overcome immune system
Persistence or Clearance:
->Acute, chronic, latent, or persistent
Clinical outcomes:
-Asymptomatic, mild, severe
Asymptomatic
Inapparent/Asymptomatic infections:
Many infections are inapparent (no signs) or asymptomatic (no symptoms)
-Signs: Objective, measurable indicators observed by clinician / pharmacist (fever, rash)
-Symptoms: Subjective experiences apparent to the patient (e.g., pain, fatigue)
Acute infections
-Short incubation periods upon virus entry
-Rapid onset of disease
-Brief period of symptoms (days to 1 week)
-Often self-limiting with a quick resolution by immunity
Acute viral infections
The range of clinical outcome
of an acute viral infection could
be wide mild, moderate, or
severe
Depending on:
-Genetic factors
-Age
-Comorbidity (other diseases)
-Individual immune response
Latent viral infections
Virus persists for long periods (or lifelong) in the host without active replication
-Evades immune detection by hiding in cells
-No symptoms, but reactivation can occur (triggered by different factors) -> common in herpesviruses
Persistent viral infections
Long-term viral presence
->Continuous or intermittent viral replication
->Can be symptomatic or asymptomatic for extended periods
Herpesvirus – latency
-Establishes lifelong infection with periods of dormancy and reactivation
-Viral genome persists in host cells without active replication
-Latency sites vary by virus type
-No viral particles produced during latency, preventing immune detection
Any viral latency is irreversible and cannot be cured or reverted!!!
Latency Establishment in HSV & VZV
Primary infection occurs in epithelial cells, causing acute symptoms ->
-Cold sore usually for HSV-1
-Chicken pox for VZV
Viruses enter sensory neurons and travel to sensory ganglia
Viral genome persists (as circular DNA) in the neuron’s nucleus -> latency
-During latency, no viral particles or symptoms produced
Herpesvirus – reactivation
->Triggered by stress, immunosuppression, UV exposure, fever, or trauma
->Virus exits latency and resumes replication in sensory neurons
->Anterograde transport moves the virus back to epithelial cells, causing symptoms
Immune system response controls the outbreak, but cannot eliminate latency
Virus and cancer
-Some cancers are induced by viruses
-Oncoviruses are viruses linked to cancer development
-Virus-induced cancers are not
contagious
-Most oncoviruses integrate their genomes into host DNA, triggering tumour formation
Mechanisms of viral-induced cancer
Mechanisms how oncoviruses induce cancer transformation:
-Encode viral oncogenes promoting uncontrolled cell divisions
-Induce conversion of cellular proto-oncogenes (normal) to
unregulated oncogenes (always active)
-Inactivate tumour suppressor genes
-Inactivate apoptosis
->Loss of checkpoint control leading to unregulated cell cycle progression
-Unsustained cell proliferation – continuous cell divisions without regulation
-Genetic/chromosome instability
Isolation and cultivation of viruses
In vitro isolation of viruses (for diagnosis) rely on their need to infect cells
-Some viruses can be cultivated using these systems in laboratory settings:
-Animal models
-Embryonated eggs (e.g. influenza vaccine production)
-Continuous cell cultures with indefinitely ability to divide in vitro
Viral quantification – viral plaque
-Cells are grown in plates, infected with viruses
-Agar or reagent overlay restricts virus spread, confining infection to neighbouring cells
-Infected cells lyse, forming localized plaques over time
-Dye staining highlights plaques, distinguishing dead cells from viable ones
-Each plaque originates from a single infectious virus, measured as plaque-forming units (PFU)
Vaccinations – principles only
Primary method to prevent viral diseases or severe cases
-Induce immune protection by targeting an external & immunogenic portion of the
virus
-Use various technologies (e.g., inactivated/attenuated viruses, protein subunits, mRNA, DNA, etc).
-Used to eradicate smallpox and it has nearly eradicated poliovirus
Antiviral drugs – principles only
To treat specific viral infections
-Interfere selectively with viral replication, being effective with minimal impact on host
cell activity, ensuring viability and safety
-Inhibit essential steps of the viral life cycle, preventing replication and spread of the virus
-To treat infections caused by specific virus
-No universal antiviral drugs are available
Human immunodeficiency virus (HIV)
Retroviridae family
-Two subtypes: HIV-1 and HIV-2.
-HIV-1 is more virulent and more infective
-Viruses that insert a copy of its RNA genome into the
host cell’s genome (lifespan chronic infection)
- HIV causes acquired immunodeficiency syndrome (AIDS), resulting in the progressive failure of the immune system
- Decrease in CD4+ T-lymphocyte count makes the body
vulnerable to life-threatening opportunistic infections (e.g.,
Cryptococcus) and cancers (e.g., oncovirus)
HIV infection and disease progression
HIV infection progresses in 3 stages:
Acute HIV: flu-like symptoms that occur days to weeks after contracting HIV
Chronic HIV: the latent and asymptomatic stage that can last several years
AIDS: occurs when CD4 cell count falls below 200 cell/mm3. This makes people vulnerable to opportunistic infections and
AIDS-defining conditions
If HIV infection is not treated, the median time from infection to the development of AIDS is 8-10 years -> HIV infection needs to be treated
HIV Combinational therapy (cART/HAART)
The highly active antiretroviral therapy (HAART): composed of -Two/three anti-HIV drugs with different mechanisms of action
Reduce viral RNA to an undetectable level
->Prevent or reduce drug resistance
->Reduce morbidity and mortality
->Prevent HIV transmission
HAART does not cure HIV infection (cannot eradicate/clear the virus from an infected individual), due to the establishment of latency (viral genome is integrated into the human genome)
