Emerging respiratory viruses

Question 1

SARS-CoV

Answer 1

• A type of coronaviruses: positive sense ssRNA genome
• All replication occurs in cytosol, none in nucleus
• Incubation time is 2-10 days
• The virus S protein (spike protein) binds to host cell surface receptor (ACE2) on the respiratory epithelium for entry
• Binding of SARS to ACE2 down regulates ACE2 expression and leads to severe lung injury and respiratory failure (ACE2 protects against lung inflammation)
• 3 phases of the infection: viral replication, immune hyperactivity, and pulmonary destruction
• SARS is systemic disease, since the virus infects many different cell types (infects immune system then disseminates to other organs)

Question 2

Signs/Sx of SARS

Answer 2

• A form of atypical pneumonia; high fever, chills, rigors, headache, dizziness, malaise, cough, breathing difficulty
• Radiography positive for pneumonia around day 7-10 of illness

Question 3

Immune response to SARS

Answer 3

• Direct infection of immune cells disrupts normal cellular function leading to lymphopenia and atrophy of lymphoid tissue
• The infection causes production of pro-inflammatory cytokines in excessive amount leading to increased severity of localized or systemic disease
• Host risk factors for a more severe illness: DM, cardiac disease, pulmonary disease, hepatitis, immunosuppression/GCC use, elderly

Question 4

Transmission of SARS

Answer 4

• Via respiratory droplets

- Also is present in sweat, urine, feces

Question 5

Origin of SARS

Answer 5

• Origin is from bats, the virus then infected civets which are eaten by some fucked up people who then contracted SARS
• Since there is an animal reservoir there is no chance at eradication
• Went from one species to another by picking up mutations to the S protein

Question 6

MERS-CoV

Answer 6

• A novel corona virus that also arose from bats
• It then infected camels, which is probably how people for it
• Transmission person-person via respiratory droplets and close contact
• Sx: fever, SOB, cough, diarrhea, vomitting
• Almost all pts have one or more chronic conditions: DM, HTN, heart disease, kidney disease

Question 7

Ebola virus

Answer 7

• Negative strand enveloped RNA virus
• Pathogenesis: first it infects dendritic cells, resulting in non-responsiveness of the T cells and reduces Abs to the virus being made
• Next it infects macrophages causing cytokine release and dissemination, including to endothelial cells and parenchymal cells
• This leads to necrosis throughout the body
• The virus inhibits the anti-viral state of the interferon pathway
• Breakdown of endothelial cells by viral glycoprotein (GP) leads to hemorrhage and shock

Question 8

Genetic disposition to ebola

Answer 8

• Survivors have a higher amount of activated T cells, high levels of proteins that allow immune cells to communicate
• There was a high level of sCD40L (blood vessel repair protein)

Question 9

Overview of hemorrhagic fever

Answer 9

• Unlike marburg virus, ebola is not culturable
• Disease is acute onset, incubation period is 2-21 days (usually 3-8)
• Starts w/ flu Sx: nausea, diarrhea, vomiting, rash
• Multiorgan failure: chest pain, SOB, bleeding, headache, confusion, seizure, coma, vomiting, diarrhea
• Main system affected: GI, resp, neuro
• The Sx and high viral load happen concurrently, so people are most contagious when showing Sx

Question 10

Current ebola outbreak

Answer 10

• Current outbreak due to Zaire strain (deadliest strain) and is so widespread b/c it is happening in one of the poorest areas of the world
• Transmission is close personal contact w/ infected body tissue/fluids
• There is a reservoir (fruit bats)