Quiz 5 Plagues and Pandemics

Dengue, Poxviruses (Mpox), Polio, Measles

What is an evolutionary tree?

A way of looking at how sequences in particular viral sequences are related

All viruses must become ___ to translate into proteins

mRNA

What does positive sensing mean? Why is it important?

With positive sensing viruses, the RNA can directly integrate into the host genome without extra steps

What does negative sensing mean? Why is it important?

With negative sensing viruses, the RNA cannot directly integrate into host genome. It must first be converted into positive sensing

What is case fatality rate?

The percent of fatal cases in a certain amount of time

What are factors of case fatality rate?

Undetected cases, comorbidity

What is basic reproduction number?

The avg number of new infections arising from one person, a way to measure contagion

What is herd immunity threshold?

The percent of a population that needs to be vaccinated/immunized to create herd immunity conditions

What are the poxviruses covered in class?

Mpox, smallpox

What is unique about poxviruses?

They are the only kind of virus that has thus far been eliminated from human populations

What kind of genome is a poxvirus?

Large dsDNA, linear genome

Where do poxviruses replicate? How?

Replicate in the cytoplasm because they have their own translational machinery (RNA polymerase) and don’t need the host cell’s.

What does the size of the poxvirus indicate?

The large genome indicates that many diverse proteins can be made, such as immunomodulators

What are the hosts of poxviruses?

Humans primarily (also other mammals)

Why can poxviruses be eliminated?

No zoonotic reservoir/human only so if virus disappears from humans, it’s gone; Similarity in structure means that if vaxx against one, also protected against others

What are introns, and why are they important to poxviruses?

Interons are pieces of genome sequences that are removed before translation. Poxviruses do NOT have interons and therefore don’t need to access host splicing material in the nucleus (links back to inter-cytokine replication)

What are immunomodulatory genes and how do they work?

Poxviruses make “decoy” receptors (immodulatory genes) to block IFN 1 binding, preventing interferon network signaling and avoiding immune response

How does smallpox transmit?

Respiratory, fomites, close contact

What is the mortality rate of smallpox?

30%

What is the history of the smallpox vaxx?

1. Variolation in ancient China

2. Edward Jenner’s milkmaid cowpox vaxx

Both involved pox scabs

What is the smallpox vaccine?

Vacciniavirus grown in chicken cells (live attn.) Immunizes against smallpox but also all other poxviruses

Who cannot get smallpox vaxx?

Immunocompromised

What was the eradication campaign for smallpox?

1979/80: Stopped vaccinating because unnecessary, also b/c formed gross pox under skin

What is the downside to the smallpox eradication campaign?

Most of the population is not immunized against smallpox, so low total poxvirus immunity. Problem if a new one comes around

What percent of the population is not smallpox immunized?

70%

Where was mpox endemic to?

Africa

What are the details of the 2022 mpox outbreak?

Started in Africa and spread in US homosexual population, controlled by vaccination campaigns

How many died in the 2022 mpox outbreaks?

88k, mostly not in the US or EU

Where did the 2022 mpox outbreak come from?

Sylvatic spillover from a squirrel

What are mpox clades?

Two “types” of mpox. Clade 1 has a higher CFR in Africa. Clade 2 spread in the US and has a lower CFR

What is the vaccine for mpox? What does it do?

JYNNEOS- vacciniavirus, protects against all poxes, also helps against transmission and symptoms

What is the focus with poxvirus vaccines?

Making something people wanna take, ex) reducing side effects and pain

Where is the burden of mpox? What does this indicate?

Highest in US, but indicates that detection here is just better than in other places (Ex Africa)

How does poliovirus spread?

Fecal oral

What are the micro characteristics of polio?

ssRNA, positive sensing (infectious genome), protein shell, no membrane or envelope

What is the purpose of the protein shell of polio?

Makes virus very stable, helps virus last on surfaces for a long time

What are the hosts of polio?

Humans

What are the mild symptoms of polio?

Mostly asymptomatic, or “Summer cold”, meningitis, diarrhea

What are the severe symptoms of polio?

Paralysis

How does paralysis with polio occur?

Polio infects neurons and gets into the central nervous system (CNS)

What is the associated disease of polio?

Polio myelitis

What are the statistics of polio myelitis and paralysis?

Happens in .5% of cases. 30% have permanent paralysis. 5-10% die when lungs are paralyzed

What is post polio syndrome?

When polio stays in the system and isn’t cleared, often 2-4 decades after initial infection. 40% of cases get this.

What is the replication process of polio?

1. Infects opharyngeal/intestinal mucosa

2. Either excreted in feces and passed OR

3. CNS infection: Passes through lymph nodes and gets into CNS through retrograde axonal transport

   1. Causes paralytic polio

What stage of polio does the vaccine prevent?

3rd stage, CNS

Why is polio so successful?

Only replicates in humans but can infect ALL humans, no cure, high asymptomatic rates, highly contagious and stable in environments

How can polio be prevented?

1. Closing public areas in summer

2. Vaccines

What are the two polio vaccines?

1. IPV, Salk, 1950, inactivated (formalin)

2. OPV, Sabin, 1960s, live attn.

   1. Grown in mouse/monkey cells

There are 3 types of polio. Which can revert to wildtype in OPV?

2 and 3- 2% nucleotide divergence in 5 days it takes to get from mouth to intestine.

What are some pros of IPV?

No revirulence risk, no spread, lifelong protection against CNS

What are some cons of IPV?

No replication = no local protection, can still be infected and spread/transmit, needs injection-trained staff, 5x cost of OPV

What are some pros of OPV?

Easy administration, cheap (IP given to WHO), intestinal replication = local protection, prevents new infection, contact immunity thru shedding

What are some cons of OPV?

Virus shed can infect naive people, revirulence risk to revert to wild type

Why is it possible for polio to be eradicated?

Good vaccines exist, only in humans, not much antigen variation, cheap and easy to produce and administer

What is the physical structure of measles?

Genome enclosed by capside, immunogenic outer proteins (hemagglutin and fusion), small 6 gene encoding

What is the burden of measles?

Worse in children and immunocompromised, which account for 20% of hospitalizations

What is the measles mortality?

1-3/1000 cases

What is the genome of measles?

ssRNA, negative sensing

How does measles spread?

Respiratory

What are the symptoms of measles?

Fever, rash, cough, diarrhea, runny noise, pneumonia

What is the disease associated with measles?

SSPE- chronic brain infection, immunosuppression and encephalitis

What is immune amnesia and how does measles cause it?

Measles destroys B and T cells in lymph nodes and destroys immune memory

Why is the destruction of lymphocytes bad?

O to opportunistic infections, immunosuppressed for years after. Nondiscriminatory between natural and vaccinated antibodies

What is the infection process of measles?

1. Enters lungs, infects m’phages and DCs (antigen presenting cells)

2. Enters lymph nodes when m’phages and DCs bring them in. Destroy memory B and T cells, 50% less antibody response

3. Back to lungs, can replicate in epithelial cells and spread now

What does SSPE cause?

7-10 years after primary infection, infection never cleared from brain. 100% fatal encephalitis.

What is the herd immunity threshold for measles?

91-94% vaccinated

What is the basic reproduction number for measles?

R0 = 15

What is case example of measles immunity?

Faroe Islands, 1864

What is the history of the measles eradication campaign?

1970s: Measles cases decrease steadily, then rise in 1990s. Two dose system introduced and standardized

What is the MMR vaccine?

Trivalent live atten. vaccine, given at 9 mo and 5 years

What percent of people got each MMR dose?

80-90% first dose, 70% second dose

What are some challenges with measles?

Getting people to take both doses, misinfo, Texas outbreak, 2014 Disney outbreak

What are the physical characteristics of dengue?

Water polo ball shell made of 3 E protein subparts

What are the genomic characteristics of dengue?

ssRNA, positive sensing. One long polyprotein cleaved into different structures

How is dengue transmitted?

Mosquito bites, aedes egypti

Dengue is “cotranslationally translated.” What does that mean?

Polyprotein is cleaved by both the viral and host proteases

What is the target of the dengue vaccine?

Eproteins

What is the burden of dengue?

Mostly equatorial/S hemisphere. About half the world is at risk. 390 mil cases yearly

In what ways has the burden of dengue changed recently?

Climate change spreads area of mosquitos, whereas dengue used to enter US thru travel, it’s now locally acquired

What are the kinds of dengue serotypes?

1, 2, 3, 4: all very different antibody responses

How did dengue get into humans?

Primate spillover

1: 300 years ago

2: 1500 years ago

4: 500 years ago

How is dengue spread?

1. Mosquito gets it from a human when biting

2. Virus replicates in mosquito gut the back into the salivary gland

3. Spread when mosquito bites another person

What is the burden of dengue symptoms?

294 mil cases are mild/asympt, 96 mil get DENV, small percent gets DHF/DSS

What are the determinants of severity of dengue?

Which dengue, if prior infected, how long ago infected

What are the symptoms of DENV?

Bone break fever, nausea, vomiting, rash, eye/bone/joint aches

How many dengue cases progress to severe?

1/20, getst shock, internal bleeding, and can die

What is dengue cross-reactivity?

When the primary infection sets up the secondary dengue infection to be worse

How does dengue cross reactivity work?

Primary infection: Antibody response, permanently protected from serotype that infected you, but all other serotype antibodies also created

Secondary infection, antibody dependent enhancement: Dengue virus uses antibodies created from primary infection to hitch rides into cells via attachment to Fc Gamma region

Why is antibody dependent enhancement so dangerous?

Abnormal route creates aberrant cytokine secretion, severe disease risk

What are the issues with dengue vaxx creation?

Need to vaxx against all 4 types of dengue at once to prevent antibody dependent enhancement

What was the early dengue vaccine, and what are pros/cons?

Dengvaxia: live attn. with all 4 serotypes, but acted as primary infection and gave way to antibody dependent enhancement. Can still be used if screen person for prior infection and they were infected already

What are the updates to the dengue vaccine?

Includes more of viral genome to allow better T cell response without immune enhancement

What is the role of bacteria in dengue treatment?

Wolbachia- wMel strain prevents virus prevalence in mosquito gut and stops transmission vector