Exam 2 PPTs - 6 Flashcards
SARS-CoV-2: …
COVID-19: coronavirus disease from 2019
- the first known case was identified in … in … The disease has since spread worldwide, leading to an ongoing pandemic
severe acute respiratory syndrome coronavirus 2;
wuhan, china;
december 2019
over the last two decades there were other outbreaks of coronavirus:
- 2003 SARS - … (…)
severe acute respiratory syndrome coronavirus 1; SARS-CoV-1
over the last two decades there were other outbreaks of coronavirus:
- 2003 SARS: SARS-CoV-1
- it infects …, … and …
- 9% mortality rate, 50% mortality rate in old individuals
humans; bats; civets
over the last two decades there were other outbreaks of coronavirus:
- 2012 MERS - … (…)
- believed to be originally from … Humans are typically infected from …
- 35% mortality rate
middle east respiratory syndrome; MERS-CoV;
bats; camels
over the last two decades there were other outbreaks of coronavirus:
- additionally, … other strains of coronaviruses are known to cause milder symptoms of …
four;
the common cold
- a virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism
- viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea
- consists of … surrounded by a protective coat of … called a … Viruses can have a … derived from the …
nucleic acid;
protein; capsid;
lipid ‘envelope’;
host cell membrane
RNA viruses: viruses that have genomes made of …
Coronaviruses: a group of related … that cause diseases in … and …
ribonucleic acid (RNA);
RNA viruses;
mammals; birds
Coronaviruses:
- the genome size of coronaviruses ranges from approximately … to … kb, one of the … among RNA viruses
26; 32;
largest
Coronaviruses: - they are found in many animal species and may/may not cause disease symptoms in their hosts - divided into four distinctive genera: 1. ... 2. ... 3. ... 4. ... These groups of coronaviruses are thought to have diverged from each other at about 2400-3000 BC 4 and tend to infect different groups of animals
alphacoronavirus (alpha-CoV);
betacoronavirus (beta-CoV);
gammacoronavirus (gamma-CoV);
deltacoronavirus (delta-CoV);
Coronaviruses:
- coronaviruses undergo frequent … If animals harboring different coronaviruses come in close contact and exchange viruses, then … can occur among the different strains, leading to …
recombination;
recombination;
diversification
Coronaviruses:
- undergo frequent recombination
- it appears that such events during the evolutionary history of SARS-CoV-2 have led to the evolution of a potent strain capable of easily infecting human cells
- in infected human samples, a study found that over 60% of all … were of viral origin (functional significance remains unknown)
transcriptomes
Evolution of SARS-CoV-2: selection:
- the closest known relative of SARS-CoV-2 is a coronavirus strain found in a … sample from Yunnan Province, China, in 2013
- the genome sequence of this strain is 96% similar to that of SARS-CoV-2
- we can compare the two sequences and calculate the ratio of … per site (dN) to … per site (dS)
bat;
nonsynonymous substitutions;
synonymous substitutions
Evolution of SARS-CoV-2: selection:
- closest known relative of SARS-CoV-2 found in Yunnan province china in 2013
- we can compare nonsynonymous substituion rate (dN) to synonymous sub rate (dS), to know if:
dN/dS < 1 replacements are …
dN/dS = 1 when replacements are … and
dN/dS > 1 when replacements are …
deleterious;
neutral;
advantageous
Evolution of SARS-CoV-2: selection:
- closest relative of covid
- the ratio of nonsynonymous substitutions to synonymous substitutions is 0.028
- the observed ratio of nonsynonymous to synonymous substitution indicates that the sars-cov-2 genome is under …
strong purifying selection
Evolution of SARS-CoV-2: selection:
- the observed ratio of nonsynonymous to synonymous substitution indicates that the SARS-CoV-2 genome is under strong purifying selection
- purifying selection: selective … of alleles that are … This can result in … selection through the purging of … that arise through …
removal; deleterious; stabilising; deleterious genetic polymorphisms; random mutations
Divergence time between SARS-CoV-2 and its closest known relative:
- to obtain a better estimate of the time of divergence of SARS-CoV-2 from other strains, it is better to use … substitutions than … substitutions
synonymous;
nonsynonymous
Divergence time between SARS-CoV-2 and its closest known relative:
- the overall percentage difference between RaTG13 and SARS-CoV-2 is 4%
- the synonymous percentage difference between RaTG13 and SARS-CoV-2 is 17%
- the rate of substitution (…) is … per year
change;
0.03
Zoonotic origin of SARS-CoV-2:
- SARS-CoV-2 is the ninth documented coronavirus that infects humans and the seventh identified in the last 20 years
- all previous human coronaviruses have … origins, as have the vast majority of human viruses
- it displays clear similarities to SARS-CoV that spilled over into humans in 2002, and again in 2003.
- both these SARS-CoV emergence events were associated with markets selling … and …, particularly … and … that were also sold live in Wuhan markets in 2019
zoonotic; live animals; involved species; civets; raccoon dogs
Zoonotic origin of SARS-CoV-2:
- SARS-CoV-2 also shows similarities to the four … human coronaviruses: HCoV-OC43, HCoV-HKU1, HCoV-229E, HCoV-NL63. These viruses have … origins, and the circumstances of their emergence are unclear
endemic;
zoonotic
Zoonotic origin of SARS-CoV-2:
- based on epidemiological data, the Huanan market in Wuhan was an early and major … of SARS-CoV-2 infection.
- Lineage B, became dominant globally, was observed in early cases linked to the …
- Lineage A contains a case with exposure to … as well as with later cases in … and other parts of China
epicenter;
Huanan market;
other markets;
Wuhan
A significant evolutionary gap exists between SARS-CoV-2 and the closest related animal viruses:
- The bat virus RaTG13 has a genetic distance of 4% (1,150 mutations) to the Wuhan-Hu-1 reference sequence of SARS-CoV-2, reflecting decades of ….
- A history of …. means that three other bat viruses - RmYNO2, RpYNO6, and PrC31 - are closer in most of the virus genome (particularly ORF1ab) and thus share a … with SARS-CoV-2
- RaTG13 is not the progenitor of SARS-CoV-2, with or without laboratory manipulation or experimental mutagenesis
evolutionary divergence;
recombination;
more recent common ancestor
A significant evolutionary gap exists between SARS-CoV-2 and the closest related animal viruses:
- no … or … for SARS-CoV-2 has been identified to date
bat reservoir;
intermediate animal
COVID: evolving threat:
- far from making people less sick, it could also evolve to become even …, as some previous viruses including the 1918 flu have. History shows the virus could evolve further to elude the …’ protective effect, although a recent study in another corona virus suggests that could take many years
- more than 2 million SARS-CoV-2 genomes have been sequenced and published, painting an exquisitely detailed picture of a changing virus
- “I don’t think we’ve ever seen that level of precision in watching an evolutionary process,” Edward Holmes
deadlier;
vaccines’
COVID: evolving threat:
- which mutations end up spreading depends on how the viruses carrying those tweaked proteins …
- the vast majority of mutations give the virus …
fare in the real world;
no advantage at all
COVID: evolving threat:
- the vast majority of mutations give the virus no advantage at all
- the … theory of molecular evolution –> kimura
- there are three kinds of mutations: …, … and …
neutral;
deleterious; neutral; beneficial
COVID: evolving threat:
- the neutral theory of molecular evolution:
- mutations that are deleterious tend to be … by natural selection
- mutations that are neutral (or nearly so) … as a result of …
- mutations that are beneficial are often … while still at low frequency, but otherwise tend to … as a result of natural selection
eliminated;
rise and fall in frequency; genetic drift;
lost to drift;
rise to fixation;
COVID: evolving threat:
- At some point early in the pandemic, SARS-CoV-2 acquired a mutation called D614G that made it a bit more … That version spread around the world; almost all current viruses are descended from it
- then in late 2020, scientists identified a new variant, now called …, in patients in Kent, UK, that was about 50% more …
infectious;
Alpha;
transmissible
COVID: evolving threat:
- …, first seen in India and now conquering the world, is another 40% to 60% more … than Alpha
- “the only way you could not get infectiousness rising would be if the virus popped into humans as … as it could be, and the chance of that happening is incredibly small”
delta;
transmissible;
perfect at infecting humans
COVID: evolving threat:
- the main metaphorical treatment is of a geographical landscape upon which evolution can ascend only … and cannot … (that is known as an …)
gradually;
climb cliffs;
adaptive landscape
COVID: evolving threat:
- alpha seems to bind more strongly to the human ACE2 receptor, the virus’s target on the …, partly bc of a mutation in the spike protein called N501Y
- in delta, one of the most important changes may be near the furin cleavage site on spike, where a human enzyme …, a key step enabling the virus to …
cell surface;
cuts the protein;
invade human cells
COVID: evolving threat:
- in delta, one of the most important changes may be near the furin cleavage site on spike, where a human enzyme cuts the protein, a key step enabling the virus to invade human cells. a mutation called P681R in that region makes … more efficient, which may allow the virus to enter more cells … and lead to greater numbers of … in an infected person
cleavage;
faster;
viral particles
Trade-offs:
- In July, Chinese researchers posted a preprint showing Delta could lead to virus levels in patient samples 1000 times higher than for previous variants. Evidence is accumulating that infected people not only spread the virus more …, but also …, allowing the variant to spread even more rapidly.
- The new variants of SARS-CoV-2 may also cause more …
- For examples, a study in Scotland found that an infection with Delta was about twice as likely to lead to … than with Alpha
efficiently;
faster;
severe disease;
hospital admission
Trade-offs:
- more …
- more …
contagious;
deadly
Trade-offs:
- The 1918-19 influenza pandemic also appears to have caused more serious illness as time went on, says Lone Simonsen, an epidemiologist at Roskilde University who studies past pandemics. “Our data from Denmark suggests it was six times deadlier in the second wave.”
- A popular notion holds that viruses tend to evolve over time to become …, allowing the host to … and … But that idea is too simplistic
less dangerous;
live longer;
spread the virus more widely
Trade-offs:
- Evolution in myxoma virus and rabbit hemorrhagic disease virus
- released in Australia in 1960 and 1996, respectively
- decimate populations of European rabbits that were destroying croplands and wreaking ecological havoc
- myxoma virus initially killed more than 99% of infected rabbits, but then … strains evolved, likely bc the virus was killing many animals before they had a chance to pass it on. It has evolved to become … over time
- Rabbit hemorrhagic disease virus, by contrast, got … over time, probably bc the virus is spread by blow flies feeding on rabbit carcasses, and … accelerated its spread
less pathogenic;
less virulent;
more deadly;
quicker death
Trade-offs:
- an assumption about human respiratory diseases may not always hold: that a milder virus - one that doesn’t make you crawl into bed- might allow an infected person to spread the virus further
- In SARS-CoV-2, most transmission happens early on, when the virus is replicating in the upper airways, whereas serious disease, if it develops, comes later, when the virus infects the … As a result, a variant that makes the host sicker might …
lower airways;
spread just as fast as before
Evasive Measures:
Researchers have worried about a third type of viral change, perhaps the most unsettling of all: that SARS-CoV-2 might evolve to evade … triggered by … or …
immunity;
natural infections; vaccines
Evasive Measures:
Researchers have worried about a third type of viral change - evading immunity
- delta is slightly more likely to infect … people than previous variants
- beta, which first appeared in South Africa, has traveled farthest on the map, although natural or vaccine-induced immunity still largely protects against I
- it’s probably the case that when a virus change to escape immunity, it loses other aspects of its …
fully vaccinated;
fitness
Evasive Measures:
- immunity reduces the likelihood of people getting infected, and may hamper …
- “that means there will be fewer mutations emerging if we …”
viral replication;
vaccinate more people
Evasive Measures:
- on the other hand, any … variant now has a huge advantage over other variants
- holmes says: with more than 2 billion people having received at least one vaccine dose and hundreds of millions more having recovered from COVID-19, variants that … may now have a bigger leg up than those that are more …
- immune escape is so worrying bc it could force humanity to …, as happens for flu
immune escape;
evade immunity;
infectious;
update its vaccines continually
Evasive Measures:
- it may already be getting harder for SARS-CoV-2 to make big gains in … “There are some fundamental limits to exactly how good a virus can get at transmitting and at some point SARS-CoV-2 will hit that plateau” says Jesse Bloom
- the known limit in the viral universe is …, which is about … times more transmissible than what we have now with Delta”
- the virus apparently faces a trade-off between … and …
infectiousness; measles; three; transmissibility; immune escape
Clues about SARS-CoV-2’s future from other coronavirus:
- cause …
- some are known to …
common colds;
reinfect people
Clues about SARS-CoV-2’s future from other coronavirus:
- cause common colds, some known to reinfect people
- immunity in recovered people wanes, or the virus changes its surface to evade immunity?
- April in PLOS Pathogens, Bloom et al compared the ability of human sera taken at different times in the past decades to … isolated at the same time or later
- They showed that the samples weren’t always effective against virus from …
- the virus had evidently … but it had taken 10 yrs or more
block virus;
10 yrs or later;
evolved to evade human immunity
Clues about SARS-CoV-2’s future from other coronavirus:
- in a preprint published this month [august 2021], researchers tinkered with the virus to learn how much it has to change to evade the antibodies generated in … and …
- it took … changes to the spike protein to escape current antibody responses almost completely
vaccine recipients;
recovered patients;
20;
Clues about SARS-CoV-2’s future from other coronavirus:
- “it seems plausible that true … is hard”
- “however, the counterargument is that natural selection is a hell of a problem solver and the virus is only beginning to experience real pressure to …”
immune escape;
evade immunity
