Lecture 11 (3 11-2021) acellular life

Unit 11: Viruses and Prions
LECTURE LEARNING GOALS
1. Define what is a virus, and describe the three theories on the origin of viruses.
2. Define and contrast prions and subviral agents. Explain how they are different from viruses.
3. Explain coronaviruses, the origin of SARS- CoV-2, how it infects cells, and the tools we use to fight the spread of COVID-19.

1. 1

2. Exam grading
•Process
–Onequestionatatime
–Check that questions are
fair, toss Qs if necessary
•Rubric
–Points for correct answers
–Points deductedforwrong
answers
–Rubric is flexible–many
correct answers!
–Points for clarity
•Strategy
–Answer the question !!
–No needtomemorize, but
some helps
–you need tousewordsand
phrasescorrectly
•Word count
–Exam 1 answers 672
–Wordlimitwas1000
–Too few words –maybe
you’re not done?
2

3. Exam grades
•Regrades
–I will regrade whole exams, just let me know--no guarantee of more points
•Perspective
–Each exam is worth 12.5% of your grade
–The difference between 88% (11.0, the mode) and 72% (9.0) is 2.0 points
–That is not even one half letter grade!
–The max points in this class is 102%, so you can also make this up!
3

4. ACELLULAR LIFE
Unit 11, 4.25.2019
Reading for today: Brown Ch. 7
4
Dr. Kristen DeAngelis
Office Hours by appointment
[email protected]

5. Unit 11: Viruses and Prions
LECTURE LEARNING GOALS
1.Define what is a virus, and describe the
three theories on the origin of viruses.
2.Define and contrast prions and subviral
agents. Explain how they are different
from viruses.
3.Explain coronaviruses, the origin of SARS-
CoV-2, how it infects cells, and the tools
we use to fight the spread of COVID-19.
5

6. Unit 11: Viruses and Prions
LECTURE LEARNING GOALS
6
1.Define what is a virus, and describe the
three theories on the origin of viruses.
2.Define and contrast prions and subviral
agents. Explain how they are different
from viruses.
3.Explain coronaviruses, the origin of SARS-
CoV-19, how it infects cells, and the tools
we use to fight the spread of COVID-19.
Poll Q

7. Virus
•Segments of DNA or RNA
encapsulated by a protein
and/or membrane
•To reproduce, it needs to infect
a cellular host, merge with its
cytoplasm or nucleoplasm, and
use the host’s cellular
machinery for replication
•Cells from all three domains of
life are susceptible to viral
infections
7
Fig 17.1. E. coli being infected by bacteriophage lambda

8. Viral diversity
•Genome size ranges 100s to millions of base pairs
•Classification is challenging
–Any shared genes can be used to generate a phylogeny
–If they are conserved evolutionarily, this tree makes a
plausible model for evolutionary history
–Because viruses are agents of horizontal gene transfer,
assuming shared genes have the same provenance is a
risky assumption!
•Two methods
–Evolutionary classification
•Introduced in Microbiology of Early Earth
–Physiological classification
•“the Baltimore method”
8

9. Hypotheses on the origin of viruses
•virus-first hypothesis
•progressive hypothesis
•regressive hypothesis
9

10. Hypotheses on the origin of viruses
•virus-first hypothesis
–Simple replicating RNA molecules, existing before the first cell
formed, developed the ability to infect the first cells.
–E.g., single-stranded RNA viruses
•progressive hypothesis
–Viruses arose from genetic elements that gained the ability to
move between cells
–E.g., Retroviruses like HIV
•regressive hypothesis
–Viruses are remnants of more complex cellular organisms
–Mimivirusesare dsDNAviruses with genomes as large as some
bacteria, and can live independent of hosts
–May be evidence of life forms after the protocelland before
LUCA
10

11. Virus- first hypothesis
on the origin of viruses
•viruses predate or coevolved with their current
cellular hosts, consistent with the RNA World
idea
•Remnants of pre- cellular life
•ssRNAviruses
•Rhinovirus (at right )
–the common cold
–ssRNAvirus
–no DNA stage
–Capsid protein coat
11

12. Progressive hypothesis
on the origin of viruses
•viruses arose from
genetic elements
that gained the
ability to move
between cells
•HIV
•Bacteriophage Mu
–Essentially a
transmissible out-of-
control transposon
12

13. Viruses as genetic offshoots of their hosts
•Plasmids
–secondary chromosomes
–differ from chromosomes in that they usually only
house non- essential genes
•Many plasmids can transfer by conjugation
,
which requires direct contact between cells
•Some plasmids are transferred via
encapsidatedintermediate, and include
genes that encode for capsid proteins and replication
13

14. HIV
14

15. Human Immunodeficiency Virus (HIV)
•ssRNAgenome
•Double-stranded DNA form can act as a
retrotransposon
•act like retrotransposons, mobile genetic
elements that make up 42% of the human
genome & can move within the genome via
an RNA intermediate
15

16. Regressive hypothesis
on the origin of viruses
•Some viruses are remnants of
more complex cellular
organisms
•Originally cellular parasites that
degenerated
–E.g., mimivirus-infected amoeba
(right)
–Similar to the obligate
intracellular bacteria
Bdellovibrio, Chlamydia, or
Rickettsia
•Evidence of life forms after the
protocell and before LUCA
16
Brown Figure 17.9

17. Mimivirus
•dsDNAvirus
•Can live independent
of hosts
–1.2 million base (Mb)
genome
–As big as bacteria!
•Klosneuvirusis another
example of the
regressive
hypothesis…
17
Brown Figure 17.8

18. Klosneuviruses
•a fourth domain of viruses?
•Phylogenetic analysis supports origins of
this group with the regressive hypothesis
18
Schulz et al. 2017

19. Virus phylogeny
•Based on core
nucleocytoplasmicvirus
orthologous genes
(NCVOGs)
–There are dozens to
hundreds of NCVOGs,
depending on the group of
organisms you choose to
analyze
–Mostly useful for large,
dsDNAviruses
19
Schultz et al. Science 2017. Transmission electron microscopy image of a candidate Klosneuvirusparticle
detected in the Klosterneuburgwaste water treatment plant biomass. Bar is 50 nm

20. Activity for Review of
Unit 11.1
1.Are the three hypotheses of the origin of
viruses mutually exclusive? Why or why not?
2.The SARS-CoV-2 virus is an RNA virus with a
small genome. What hypothesis of origin does
this virus represent, and why?
20

21. Unit 11: Viruses and Prions
LECTURE LEARNING GOALS
21
1.Define what is a virus, and describe the
three theories on the origin of viruses.
2.Define and contrast prions and subviral
agents. Explain how they are different
from viruses.
3.Explain coronaviruses, the origin of SARS-
CoV-19, how it infects cells, and the tools
we use to fight the spread of COVID-19.
Poll Q

22. Prions are abnormally folded
proteins who’s form is infectious
22
Figure 17.12 PrP
C
(normal, left) and PrP
Sc
(diseased, right)

23. Prions form amyloid plaques
•Crystalline aggregates of abnormal proteins recruit
more normal proteins to the abnormal, misfolded,
disease conformation
23

24. Prions
•misfoldedproteins
which are the agents
of infectious disease
•Creutzfeldt-Jakob
disease (CJD)
•Transmissible
spongiform
encephalopathies
(TESs), including
bovine SE or mad
cow disease
24
Figure 17.10 Sheep with scrapie, disease caused by prions

25. Causal hypotheses
of prion diseases
•Protein-only hypothesis
•Genetic factors
•Heavy-metal poisoning
hypothesis
•Viral hypothesis
25

26. AcellularLife
•Prions
–Abnormally folded proteinsthat are transmissible to other
normally-folded proteins, inducing their abnormal folding
–disease symptoms are similar to viral infection
•Viruses
–DNA or RNA encapsulated in protein and/or membrane
that require a cellular host for some portion of it’s life cycle
•Viroid
–Smallest known infectious agents
–Usually circular ssRNAwithout a protein coat or capsid
•Satellite
–subviral agent composed of nucleic acid
–depends on the co-infection of a host cell with a helper or
master virus for its replication
26

27. Viruses vs. Subviral agents
•Depends on the co-infection of a host cell with a helper
or master virus for its replication
27
Virus Viroid Satellite
ReplicationDirects host cell to helpDirects host cell to helpDepends on helper
virus to direct host cell
Genome DNA or RNA orboth (if
alternating during its life
cycle)
CircularssRNA DNA or RNA
Genome
size
10,000 –2M base pairs200–400 basepairs 220 –1,500 base pairs
StructureProtein shell or capsid
encasesthe genome,
sometime also an
envelope
Genomeencodes no
proteins; transmitted as
RNA particles
Protein shell or capsid,
often needs helper
Host rangeBacteria, Archaeaand
Eukaryotes
Plants Plants (most
common),mammals,
arthropods, bacteria

28. Activity for Review of
Unit 11.2
•Explain how prion disease is transmitted.
Based on how you know it works, come
up with at least three ideas about how
prion disease could be treated.
28

29. Unit 11: Viruses and Prions
LECTURE LEARNING GOALS
29
1.Define what is a virus, and describe the
three theories on the origin of viruses.
2.Define and contrast prions and subviral
agents. Explain how they are different
from viruses.
3.Explain coronaviruses, the origin of SARS-
CoV-2, how it infects cells, and the tools
we use to fight the spread of COVID-19.
Thanks to Rachel Mackelprangfor many slides & slide ideas in this section
https://www2.slideshare.net/RachelMackelprang/novel-coronavirus-information

30. Coronaviruses
•Coronavirus commonly affect
humans, & cause ~20% of
common colds.
•Since 2003, there have been
three “spillovers” of an animal
coronavirus to humans
–Severe Acute Respiratory
Syndrome (SARS-CoV)
–Middle East Respiratory
Syndrome (MERS-Cov)
–2019 “novel coronavirus,”
•virus name SARS-CoV-2,
•disease name COVID-19
30
Illustration of a coronavirus
Red: spike proteins (S)
Grey: lipid bilayer envelope
Yellow: envelope proteins (E)
Orange: membrane proteins (M)
https://www.nytimes.com/2020/04/01/health/coronavirus-illustration-cdc.html

31. Ground Zero
•~11 million people
•Central China’s political, economic, financial,
commercial, cultural and educational center
•Major transportation hub
31
https://www.sciencemag.org/news/2020/01/novel-human- virus-pneumonia-cases-
linked-seafood-market-china- stir-concern

32. Relationships between coronaviruses
•…
32
Zhou, P., Yang, XL., Wang, XG.et al.A pneumonia
outbreak associated with a new coronavirus of
probable bat origin.Nature579,270–273 (2020).
https://doi.org/10.1038/s41586-020-2012-7
Common human coronaviruses
SARS
MERS

33. Animal Origins
•Bats are common CoVreservoirs
•Bats and Pangolins are the prime
suspects, but bats are the more
likely source.
•Different scenarios of cross-species
transmission will exhibit different
phylogenetic patterns (C)
33
Han, Guan-Zhu. "Pangolins Harbor SARS-CoV-2-
Related Coronaviruses."Trends in Microbiology(2020).

34. Coronavirus genome
34
•32 kbpgenome, ssRNA(+) sense
•One of the largest known RNA virus genomes
•Able to mutate and change at a high rate

35. How coronavirus infects your cells
35https://www.nytimes.com/interactive/2020/03/11/science/how-coronavirus-hijacks- your-cells.html
Spike proteins bind to your ACE receptors
in the lining of your airway
ACE receptors

36. How coronavirus infects your cells
36https://www.nytimes.com/interactive/2020/03/11/science/how-coronavirus-hijacks- your-cells.html
Viral RNA
Viral RNA is released into
the cell and translated in the
human cells
Viral RNA
Viral Protein

37. Making new viruses
37https://www.nytimes.com/interactive/2020/03/11/science/how-coronavirus-hijacks- your-cells.html
Host Cell
Nucleus
Viral Proteins produced

38. Making new viruses
38https://www.nytimes.com/interactive/2020/03/11/science/how-coronavirus-hijacks- your-cells.html
New virus particles are packaged…
…and released, where they infect
other cells and individuals

39. Your immune system responds
39https://www.nytimes.com/interactive/2020/03/11/science/how-coronavirus-hijacks- your-cells.html
Flu vaccine
Flu antibody
COVID
vaccine
COVID antibody

40. Official counts as of 26 January 2021
•Globally, there have been99,363,697 confirmed casesof
COVID-19, including 2,135,959deaths, reported to WHO.
40

41. •Globally, there have
been99,363,697
confirmed casesof
COVID-19, including
2,135,959deaths,
reported to WHO.
•In the US, there have
been24,916,899
confirmed casesof
COVID-19 with
416,004deaths.
41
Official counts as of
26 January 2021
SARS-CoV-2
Pandemic
2.6M

42. Genomic Epidemiology
•use of genetic sequences of pathogens to
understand patterns of transmission spread
42
Information and figures from Trevor Bedford (https://bedford.io/blog/) and
the awesome Nextstrainproject (https://nextstrain.org/ncov)
On average, there is a 7 day interval from one infection to the next
On average, the virus mutates ~2 times per month. This means that
~every other step in the transmission chain will have a mutation.

43. Genomic Epidemiology
•use of genetic sequences of pathogens to
understand patterns of transmission spread
43
Information and figures from Trevor Bedford (https://bedford.io/blog/) and
the awesome Nextstrainproject (https://nextstrain.org/ncov)

44. Global SARS-CoV-2 as of 19 Jan 2021
44

45. Global SARS-CoV-2 as of 9 Mar 2021
45

46. Global SARS-CoV-2 as of 9 Mar 2021
46

47. How is COVID-19 spread?
•spreads very easily from
person to person
•most commonly spreads
during close contact
•can sometimes be spread
by airbornetransmission
•spreads less commonly
through contact with
contaminated surfaces
•rarely spreads between
people and animals
•Spread depends on
–The virus
–Social settings
47
https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/how-covid-spreads.html
https://www.bbc.com/news/world-53329946

48. How quickly does it spread?
•This depends partly on the R
0(pronounced “R naught”)
•R
0is the basic reproduction number, an estimate of the
number of people who catch the virus from a single
infected person.
SARS- CoV-2 R
0= 2.6. Seasonal flu R
0= 1.3
48

49. How quickly does it spread?
•This also depends on social
interactions
•Social distancing limits the potential for spread
,
slowing the overall
infection rate as well as the
mutation rate of the virus.
•This simulation shows viral
spread over time with
colors for healthy, infected
and recoveredindividuals
49
https://commons.wikimedia.org/wiki/File:Simulation_social_distancing_2.gif

50. How is it spread?
•Sketch showing arrangement of restaurant tables and air conditioning
airflow at site of outbreak of 2019 novel coronavirus disease,
Guangzhou, China, 2020. Red circles indicate seating of future case-
patients; yellow-filled red circle indicates index case-patient
50
https://wwwnc.cdc.gov/eid/article/26/7/20-0764_article

51. How is it spread?
•Air flow affects potential transmission of exhaled particles from normal
respiratory behaviors. “Our results show that the design of ventilation is
critical for reducing the risk of particle encounters.”
51
Flow Field Imaging Lab, UMN https://arxiv.org/abs/2007.03645

52. Where are you likely to acquire it?
•Adjusted odds ratio
(aOR)* and 95%
confidence intervals
for community
exposuresassociated
with confirmed
COVID-19 among
symptomatic adults
aged ≥18 years (N =
314) —United States,
July 1–29, 2020
52
https://www.nytimes.com/2020/04/20/health/airflow-coronavirus-restaurants.html
https://www.cdc.gov/mmwr/volumes/69/wr/mm6936a5.htm?s_cid=mm6936a5_w#:~:text=Adults%20with%20positive
%20SARS-CoV,-CoV-2%20test%20results

53. How deadly is COVID-19?
53
https://www.nytimes.com/interactive/2020/world/asia/china-coronavirus-contain.html
note the
log scale !
Average number of people infected by each sick person (R
0)
Fatality rate (%)
Estimates range between
0.1% and 3%
Caveat: Very difficult to
determine lethality of new virus.
Worst cases are usually
detected first, which can skew
estimates. People with mild
illness may never visit a doctor.

54. Who gets infected with SARS-CoV-2?
•People of ANY AGE are equally susceptible
to being infected with SARS-CoV-19
•Vaccinated people can still get infected
–Vaccines do not confer immunity right away, it
takes a few weeks for your body to build the
antibodies
–Vaccines are only ~95% effective
•The vaccine cannot give you the virus!
54

55. Who is the most vulnerable?
•COVID-19 is far more
deadly for older
population than the flu
•COVID-19 is more fatal
across all age groups
than seasonal
influenza
•COVID-19 is affecting
Black, Indigenous,
Latinx, and other
people of color the
most.
•Racial inequality in
mortality is due to
systemic racism
55
https://www.cdc.gov/coronavirus/2019-ncov/community/health-equity/race- ethnicity.html
https://covidtracking.com/race

56. Who is the most vulnerable?
•80% of cases are mild, but there are underlying conditions
associated with severe cases of COVID-19
56
These conditions are common
across ALL age groups and can
increase risk in individuals other
than the elderly and infirm.
https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html

57. Symptoms
57

58. We have vaccines!
•…
58
https://www.cnn.com/2020/11/24/health/covid-vaccines-design-explained/index.html

59. 59
https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html

60. Variants
Variants of Concern: Coronaviruses that appear to be
more infectious than other circulating coronaviruses.
Left, SARS-CoV-2 genome. Right, the 20I/501Y.V1 lineage, aka B.1.1.7.
https://www.nytimes.com/interactive/2021/health/coronavirus-variant-tracker.html
60

61. Vaccines are being tested
against new variants
•Because the vaccine
mechanism is encoded
in the spike protein
mRNA, the vaccine is
quite modular
61
Image courtesy of Eric Martz, Protopedia.Org , https://proteopedia.org/w/SARS-CoV-2_spike_protein_mutations
Spike protein priming reveals the ACE2 binding
site. The COVID-19 spike protein is a homotrimer,
with each chain a different color. There are four
mutations in lineage B.1.1.7;ACE2 binding
site;furin(protease) cleavage site.

62. How can I protect myself?
62

63. Safe masks
•Make sure your mask:
–fits snugly but comfortably
against the side of the face
–completely covers the nose
and mouth
–is secured with ties or ear loops
–includes multiple layers of
fabric
–allows for breathing without
restriction
–can be laundered and
machine dried without
damage or change to shape
63
Lots of studies show that masks keep *you* safe:
https://www.cdc.gov/coronavirus/2019- ncov/more/masking-
science-sars-cov2.html?fbclid=IwAR28PppCa6x2uxwO8Z2baHM0KHS4JXx0inzzMQs3zRHV1qql_0a8mxZfpCw
Good mask, bad mask

64. Soap Kills Coronavirus
64
SLS competes with lipids and “punches
holes” into the membrane
and
It substitutes interactions of virus
proteins/membrane with molecules on skin
Sodium lauryl sulfate (SLS, C12), the main detergent
in hand soap, is an amphipathic(has hydrophilic
and hydrophobic part) molecule. Just like lipids!
Lipid
membrane

65. Activity for Review of
Unit 11.3
•Explain the COVID-19
meme to the right.
•EXTRA CREDIT:Design
your own COVID- 19
vaccine (or other public
health) meme
–1 or 2 points for accuracy,
novelty, creativity &
message
–Upload to Moodle and follow
instructions
65

66. Unit 11: Viruses and Prions
LECTURE LEARNING GOALS
1.Define what is a virus, and describe the three
theories on the origin of viruses.
2.Define and contrast prions and subviral agents.
Explain how they are different from viruses.
3.Explain coronaviruses, the origin of SARS- CoV-2, how
it infects cells, and the tools we use to fight the
spread of COVID-19.
This is the last class! Thank you for your time & attention.
•Review session, TBD
•Email me ([email protected]
) if you want to discuss anything
further.
66