Quiz 6 Plagues and Pandemics

RSV, Flu 1/2/3, HIV/AIDS 1

What sense and genome is RSV?

RNA, negative sensing

What are the hosts of RSV?

Humans, cattle, rodents, chimps

Recall the replication cycle of a virus

Attachment, fusion, replication, mRNA transcription, protein translation, assembly/budding

What part of the lungs does RSV infect?

Epithelial cells

What is the burden of RSV?

Usually by age of 1, but everyone infected by ages of 2-3. Worst for babies and old people as per usual

What makes RSV so infectious?

No lifelong protection and continually reinfected throughout life

What age group gets upper respiratory RSV?

Only adults

What age group gets lower respiratory RSV?

All can, but especially babies

Why are babies so susceptible to RSV?

Immunity depends on mother

What are other contributing factors to RSV?

Seasonality (cold season), behavioral (low rates during COVID)

What do RSV vaccines target?

F fusion glycoprotein and G glycoprotein, surface proteins

What are the issues with RSV vaccine development?

• Short time to vaccinate babies before infection since happens so quick

• Evades innate immunity and dampens immune response

• Natural immunity does not prevent infection

• Vaccine can actually worsen illness

What is a unique characteristic about the RSV fusion protein? What does this have to do with RSV vaccine making?

Fusion protein anchors host and viral cell membranes for fusion, changing shape multiple times during this process. This makes vaccine development difficult as vaccine can only recognize one form of fusion protein

What is the prenatal solution for RSV?

Vaccinate mother and let her antibodies against RSV be passed on to the baby; passive immunity

What happened with the 1960s RSV vaccine?

Enhanced illness because it didn’t neutralize viral antibodies, instead antibodies formed inflammatory deposits in lung tissue

What technologies are vital to the current RSV vaccine?

1) Protein structure understanding

2) mRNA

What is important to know about RSV’s protein structure?

There are two forms: pre- and post-fusion. Post-fusion, the antibody binding sites that vaccines bind to fold into the protein, hiding it from any vaccine. In other words, vaccines won’t work on post-fusion form of RSV

How does the RSV vaccine prevent post-fusion structure formation?

Amino acid mutations to force the protein to stay in its pre-fusion form

Who receives this RSV vaccine?

1) Pregnant mothers

2) Adults over 75

What is another way to treat RSV?

Monoclonal anitbody given to baby after birth if mother not vaccinated

What kind of sensing and genome is influenza?

ssRNA, negative sensing

What is influenza’s method of transmission?

Respiratory

What is the shape of influenza?

Spherical or filament

How many genome separations and proteins does influenza code for?

8 separations, 11 proteins

What is the life cycle of influenza?

Needs endocytosis for host pH to drop enough to facilitate fusion inside the host cell, mediated by HA

What are the glycoproteins of influenza?

HA (hemogglutanin) and NA (neurominadase)

What is the role of HA in influenza?

Binding and fusion

What is the role of NA in influenza?

Enzymatic activity, cleaving scialic acid connections so flu can leave infected cells

Which HAs and NAs infect people?

H1-3, and N1 and N2

What are the hosts of influenza?

Humans and primates, aquatic birds (fecal-oral)

Which influenzas are responsible for human flu?

Mostly A, some B

Which flu causes pandemics?

A

Why is flu A the most common influenza?

Wide host range, close animal contact, constant zoonotic spillover, high infection rate

What is the role of scialic acid with influenza?

Flu receptor on host cells, fuses its glycocalyx and HA on flu virus. NA cleaves this connection so flu can exit an infected cell

What does influenza pathogenesis look like?

Lower respiratory more severe, replication peaks after 2 days, doesn’t shed much after 6-8 days

How can influenza cause death?

Secondary infections

What cells does influenza infect?

Epithelial, macrophages. Cytokine storm makes infection worse

What is the annual burden of influenza?

1 bil infected, 3-5 mil severe, 500k deaths

What is the pattern of influenza?

Winter (in either hemisphere), constant rate at equator. Moves across equator

How can influenza replicate and form new HA/NA combos?

When genome breaks into different segments, they can reassort to make new combinations. This happens when one cell is infected with two different flu strains

What is the role of HA with influenza replication?

Major target for antibody receptors and mediates binding, which puts pressure on it to mutate to escape immune system

What is antigenic drift?

Single nucleotide changes in influenza

What is antigenic shift?

Influenza genome reassortment and recombination, larger change

What are the characteristics of antigenic drift?

Epidemics, some cross-protection, causes seasonal annual flu, selection for escape from neutralizing antibodies

What are the characteristics of antigenic shift?

Causes major pandemics, no cross-protection, only Flu A because Flu B doesn’t spread with animals, caused Spanish Flu, HA and NA combination shuffling

What was the Spanish Flu?

1918 flu pandemic of H1N1 among WW1 troops and Native populations especially. Closely related to avian flu, a jump of new HA/NA

Was Spanish Flu a shift or drift?

Shift, but NOT reassortment

What was the burden of Spanish flu?

Young adults had it worse because no immunity from older peoples’ prior H1 exposure

How did Asian Flu and HK flu spread?

Asian flu: H3N2 birds + H1N1 humans = human H2N2

HK flu: H3N2 birds + H2N2 humans = human H3N2

What are the characteristics of the current influenza vaccine?

Trivalent (H1N1, H3N2, Flu B strain)

What is the efficacy of the influenza vaccine?

~60% is pretty good

How is the virus for the flu vaccine chosen?

Based off other hemisphere’s major outbreaks

How is the flu vaccine grown?

HA/NA + chicken growth enzymes → chicken eggs, attenuated then killed virus

What are some cons to egg-grown influenza vaccines?

Poultry allergies, avian disease could wipe out the eggs

Why is avian flu so bad?

Waterfowls are reservoir for all HAs and NAs. Birds grow scialic acid 2-3 in their intestinal tracts, which infects humans in their lower respiratory system

What scialic acid causes seasonal flu?

2-6

When could avian flu H5N1 become a risk?

If humans work closely with poultry, but so far is a dead end in humans

Why is H5N1 a concern?

Showing up in more birds and in mammals, show it has an aptitude for host switching

What is a possible positive for H5N1 in humans?

We may have some cross-protection because of the N1

How can humans be protected against H5N1?

Prevent reassortment of avian flu with human flu by vaccinating farmers with normal flu vaccine

What is the genome and sensing of HIV?

ssRNA, positive sensing

What kind of virus is HIV?

Retrovirus, meaning it encodes reverse transcriptase

What kind of forms of HIV are there?

Immature (noninfectious) and mature (infectious)

What are the hosts of HIV?

Humans, primates

How is HIV transmitted?

Body fluids (breast milk, sexual fluids, blood)

What is the associated disease of HIV?

AIDS

What does AIDS target?

CD4+/ T helper cells

What is the burden of HIV?

10s of millions have died, 40 million currently living with it

What percent of the population of the world has HIV?

0.7%

What percent of Africa has HIV?

3.1%

How many new HIV infections are there annually?

1.3 million

Where did HIV come from?

Was a zoonosis, from SIV in old world primates to hominids (chimps) to humans

What is the most common form of HIV?

HIV-1 Clade M

How did HIV spillover occur?

Butchering of chimp bush meat, blood contact

Which form of HIV is more pathogenic, -1 or -2?

HIV -1

When did HIV spill over?

Early 1900s

What is the rough timeline of HIV?

1981- Public health officials note aggressive, rare cancers in young men

1982- AIDS defined, blood transfusion cases

1983- HIV id’d as source oc AIDS, UCSF Ward 86

1985- Reagan acknowledges HIV/AIDS

1987- AZT and ACTUP

1992- AIDS is #1 cause of death in young men, 19-45