Lecture 6 - Viral Pathogenesis - Virology

Lecture Objectives

• Main Objective: Understanding how viruses induce disease in hosts

• Elements Covered:

  • Overview of viral pathogenesis

  • Inapparent infections

  • Steps in viral pathogenesis

  • Human viral entry points

  • Spread of viruses

  • Viral transmission

Hosts for Virus Replication

• Key Concept: Genomes establish themselves in host for long-term survival.

• Major Themes in Virology: What factors prevent viral establishment in hosts?

Host Immune System

• Three Levels of Defense Mechanisms:

  • Skin barrier

  • Internal immune responses

  • Pathogen communication strategies

• Successful pathogens can evade these defenses, leading to continued viral replication.

Inapparent Infections

• Definition: Infections that activate the immune system but show no major symptoms.

• Key Facts:

  • Replication and transmission are likely, depending on the virus type.

  • These infections underscore the concept of inapparent infections.

Case Study: West Nile Virus

• Overview:

  • Family: Flaviridae, Virus type: + RNA with envelope

  • Transmission: Spread by mosquitoes

  • First North American Case: 1999, NYC, NY

• Impact: Led to a significant public health response—7 deaths in an epidemic risk.

  • Initial confusion by CDC on testing methods for a novel virus led to the spraying of insecticides.

Symptoms of West Nile Virus Infection

• Overview of Symptoms:

  • 80% of infected individuals experience no symptoms.

  • 20% exhibit acute symptoms.

  • 1% may develop neuroinvasive illness, potentially fatal.

  • Note: Virus can be transmitted through blood; donors must be cautious.

• How was it studied

  • do sequencing to se if genome is present in blood sample or in mosquito

  • Phylogenetic tree will give us various sequences

    • able to analyze west Nile virus strains that are circulating in the world

    • closer terms are together closer the genomes will be between the two different strains

First Virus known to cause disease in humans

• yellow fever

• solders were dying

  • something in mosquitos that are causing the solders to die

• got healthy volunteers and injected venom of mosquitos into them to study the immune response and viral load, allowing us to understand how the virus interacts with the human immune system.

Viral Pathogenesis, questions?

• start w susceptible and permissive cells

• amount of virus needed to infect varies by person due to age and immune response and if they have already been infected

• when virus is cleared we can still have miserable symptoms bcs our immune system has been activated to such a high degree

• fenner injected virus into foot of animal… 9 days later foot is swollen, indicating a local inflammatory response but the systemic effects of the virus were also observed, as the animal exhibited signs of fever and lethargy, demonstrating that the virus had disseminated beyond the initial site of infection.

• viremia - viral infection is travelling through the blood of the animal resulting in widespread distribution of the virus to various organs and tissues, which can lead to more severe clinical manifestations.

• Primary viremia

  • often end up in areas such as the spleen and liver

• secondary viremia

  • blood is still around these organs which can lead to the infection and inflammation spreading to different parts of the animal

Viral Entry Points (Human Hosts)

• Mucosal lining is found in all of our respiratory alimentary and urogenital tracts

  • distinct cells in eyes also manages entry of pathogens

• Primary Routes for Viral Entry:

  • Skin (when breached)

  • Mucosal linings (respiratory, alimentary, urogenital tracts)

  • Conjunctiva (eye)

Specific Pathways for Viral Entry

Skin

• Skin acts as a physical barrier; the epidermis comprises dead cells, creating an unfavorable environment for viruses.

• Can be breached by:

  • Insect bites

  • Needle punctures

• virions can be inactivated by acidic pH on skin , which serves as a protective barrier against many pathogens.

• epidermis is a horrible breading ground for viruses

Respiratory Tract

• Entry through Aerosolized Droplets:

  • Viruses often enter via coughing, sneezing, or contact with saliva.

  • Examples: Rhinovirus, Influenza virus

Alimentary Tract

• Entry via Food:

  • Viruses must survive acidic conditions.

  • Examples: Reoviruses, HIV (lower tract entry via anal intercourse).

• viruses will survive differentially depending on what area they enter… entering through mouth can be destroyed by stomach acid

  • hiv enters through mouth it will be destroyed

  • if entered through fecal route then it can survive longer as it passes through the gastrointestinal tract, where it can replicate and potentially lead to systemic infection.

Urogenital Tract

• Examples of Viruses:

  • Retrovirus (HIV), Human Papilloma Virus

  • Low pH and mucus provide some barriers but abrasions enable entry.

Conjunctiva

• The eye is susceptible to viral infection; blinking serves as a mechanical defense.

• Example of Viruses: Certain adenoviruses can infect the conjunctiva.

Concepts of Virus Shedding

• Definition: Release of virions from an infected individual, crucial for transmission.

• Methods of Shedding:

  • Aerosol secretions (coughing, sneezing)

  • Feces, blood, urine, milk, skin lesions.

Transmission Modes of Viruses

• Types of Transmission:

  • Iatrogenic: Healthcare worker to patient

  • Nosocomial: Infection within a hospital

  • Vertical: Parent to offspring

  • Horizontal: Transmission between individuals.

Summary of Viral Pathogenesis using Hepatitis A as an Example

• Transmission: Exceptionally high incidence in certain populations due to contaminated shellfish.

• Process Overview:

  • Entry through the alimentary tract

  • Initial immune response

  • Viral replication leads to spread in the body

  • Shedding in feces contributes to further transmission.