Microbiology Exam 3 Module 5.2

Viral Polymerase Advantages

________________________ of ________ polymerases: 1. Viral polymerases can evolve traits that better meet the needs of its own replication - When we look at viral polymerases, we see that they tend to go faster so they can generate mRNAs and genome copies faster than host polymerases could, they also tend to help lower accuracy, which generates frequent variance, and this is good because it promotes fast evolution of viral strains 2. Additionally, the virus doesn't need to gain access to the nucleus - The nucleus of a host cell is guarded by nuclear pore complexes, so viruses that have to get into the nucleus must have specific strategies and often special accessory proteins that allow them to access the nucleus 3. Finally, they can infect cells that are not actively replicating - In eukaryotic cells, DNA polymerase is only active when cells are preparing to divide - If a cell is not in the right phase of the cell cycle and its DNA polymerase isn't active, then a virus isn't going to be able to replicate in that host cell

Group 4 Viruses

(+) Sense Single-Stranded RNA Viruses The genomic RNA looks like mRNA (+ sense RNA) - It can be translated directly by host cell ribosomes For these viruses, the first thing that happens upon entry into a host cell is the genome serves as a template for translation of the viral RNA dependent RNA polymerase - Once this RNA polymerase is produced, it can then use the genome as a template for producing anti-sense RNA (- sense RNA) --> It uses the + sense RNA as a template to build the complimentary anti-sense strand --> That anti-sense strand is then used by the same RNA dependent RNA polymerase as a template to make more + sense RNA --> This step synthesizes copies of the + sense RNA that can be packaged into new virions The + sense RNA Is also mRNA - This step not only replicate the genome, but it also generates more copies of mRNA, that can be translated by ribosomes to produce the capsid viruses For these viruses, the first step is the synthesis of the viral RNA polymerase in order to both replicate the genome and synthesize more mRNA that can be translated The big difference between Group IV and Group V viruses is that Group IV viruses have RNA polymerase encoded in their genome, and do not need to carry in the functional enzyme, whereas Group V viruses have RNA polymerase encoded into their genome, and they also have to carry the functional enzyme into host cells with them

Group 5 Viruses

(-) Sense Single-Stranded RNA Viruses Their genomes are - sense, so they enter a host, and the RNA strand is complimentary to the viral mRNA - The genome cannot be translated directly upon entry into a host cell - Instead, the genomic RNA must serve as a template for the production of mRNA, but production of RNA from an RNA template requires a viral RNA dependent RNA polymerase --> - sense RNA viruses must carry this enzyme in with them, and that polymerase has to enter the cell with the viral genomes that it can be used in the first step In the virion, the viral RNA dependent RNA polymerase is packaged with the RNA genome - The viral RNA polymerase uses the - strand genome to synthesize the + strand --> That + strand is then used as a template for translation of viral proteins --> From that mRNA, capsid proteins are synthesized as well as copies of the RNA polymerase enzyme that can be packaged into new virions --> The + strand that was synthesized in step 2 is also used as a template for making copies of the - strand genome --> That same viral polymerase synthesizes many copies of the genome that can then be packaged into new virions The big difference between Group IV and Group V viruses is that Group IV viruses have RNA polymerase encoded in their genome, and do not need to carry in the functional enzyme, whereas Group V viruses have RNA polymerase encoded into their genome, and they also have to carry the functional enzyme into host cells with them

Humans

-In ______________, the sialic acid is linked by an alpha-2,6 linkage

Pigs

-In ______________, the sialic acid is linked by both an alpha-2,6 linkage and an alpha-2,3 glycosidic linkage

SARS-CoV

2003 Novel human coronavirus first found in late 2002 when cases of a mysterious pneumonia-like illness began occurring in the Guangdong Province in Southeastern China The disease was named Severe Acute Respiratory Syndrome or SARS and was characterized by headache, fever, chills, muscle aches, diarrhea, cough, chest pain, shortness of breath, and complications leading to fatality. - Scientists identify the culprit as a strain of coronavirus and found genetically similar viruses in the masked palm civet, which is a small, cat-like mammal that is treated as a culinary delicacy in some parts of China and they're sold in Guangdong's animal markets. - Later surveys revealed large numbers of SARS-related coronaviruses circulating in China's horseshoe bat population and so that suggested that the deadly strain probably originated in bats and then later passed through civets before reaching humans and then once in humans, it was transmitted from human to human through respiratory droplets and direct contact. The SARS outbreak triggered a global emergency as it spread to 26 countries, infecting about 8,000 people worldwide and killing about 800 people. - The mortality rate was pretty high, it was about 10 percent. - The outbreak was contained by case surveillance, isolation of patients, contact tracing, and strict enforcement of quarantine. - By interrupting all human to human transmission, SARS was effectively eradicated in about eight months after the original outbreak occurred. When SARS emerged, it was really concerning because it's a coronavirus with a 10 percent mortality rate, and prior to SARS, coronaviruses had never been implicated in such severe disease, they were only known to cause the common cold. The main question was, how and why does this strain cause such severe disease compared to the strains that typically cause the common cold. - Well, one of the explanations has to do with the evolution of the spike protein to bind a novel host receptor, allowing it to infect cells deep in the respiratory tract such that it can cause viral pneumonia. --> The spike protein mediates host cell attachment and entry and the receptor binding domain of the spike protein is poorly conserved among different coronaviruses, and so as a result, host receptor usage varies pretty widely between viral species. - SARS was found to bind to a receptor called ACE2, which is expressed on lung epithelial cells and enterocytes of the small intestine, so the cells that line your small intestine and that means that the SARS coronavirus could cause a viral pneumonia because of its ability to infect cells deep in the respiratory tract and it can also cause gastrointestinal symptoms like diarrhea because ACE2 is expressed on intestinal cells. --> The common cold coronaviruses use different receptors that are found in the upper respiratory tract only and so they only cause mild respiratory illness rather than viral pneumonia

MERS-CoV

2012 Novel human coronavirus first found in 2012 when a 60 year-old patient in Saudi Arabia died of pneumonia and kidney failure. - The disease was termed Middle East Respiratory Syndrome, or MERS Analysis of past samples show that the virus may have been circulating in camels since the early 1980s, and MERS related viruses have been found in bat species on five continents, suggesting a spillover event from bats to camels to humans. - MERS binds to a different receptor than SARS - SARS binds to ACE2, MERS binds to a receptor called DPP4, which is expressed in lung cells but also in kidney cells, which explains the possible kidney failure associated with MERS infection. MERS originated in Saudi Arabia, and then spread to 27 countries. - There were about 2500 cases and about 850 deaths, meaning MERS had a case fatality rate of almost 35 percent, --> MERS was really deadly. Thankfully, it doesn't transmit easily from person to person unless there is sustained close contact, 80 percent of human cases have been reported by Saudi Arabia. - Cases outside the Middle East are usually people that were infected in the Middle East and then left. - There have been small outbreaks that have occurred among families and in health care facilities, but no sustained human-to-human transmission has been documented anywhere in the world. - Experts believe that it takes prolonged exposure to MERS to sicken people and so poor ventilation in hospital rooms or close contact within families can explain why outbreaks happen in hospitals and among families. Another important feature of MERS is that about 75 percent of MERS cases had some kind of underlying disease, and so it seems like it takes a lot of virus to infect you and you have to be pretty sick to begin with to succumb to it. - It's deadly if it can establish infection, but thankfully it's not very good at establishing infection.

SARS-CoV-2

2019 Novel human coronavirus first found in 2019 when a bunch of people became sick with atypical pneumonia after visiting the Wuhan seafood wholesale market. - There was a cluster of 27 pneumonia cases, seven of them were very severe and they were reported by the Wuhan Municipal Health Commission on December 31st, 2019. - On January seventh, 2020, it was announced that the causative agent was a novel coronavirus and the associated disease was termed COVID-19 It has a similar genome and uses the same host receptor as SARS-CoV - Genome sequencing revealed close similarity between the genome of the novel coronavirus and SARS-CoV classic, giving it its name - It was also discovered pretty quickly that the novel SARS virus uses the same host receptor as this strain, so it also binds to ACE2, which explains the potential of COVID-19 to progress into severe viral pneumonia. - Obviously the extent of COVID-19 quickly surpassed the SARS and MERS epidemics Last March, March 26th, 2020, we had hit 500,000 confirmed cases worldwide. - By June, we were up to 6 million cases worldwide, and a year into the pandemic we hit a 121 million cases worldwide. - We know that SARS-CoV-2 is highly transmissible and it spreads rapidly among human populations. It's not as deadly as SARS classic or MERS. - If we take the number of fatalities and we divide that by the number of confirmed cases, we get a mortality rate of about two percent. - But that does not include all the cases that were not reported, so anyone that had an asymptomatic case or a case that was so mild that they didn't get tested, would not be included in this total case number, so the mortality rate is likely much closer to one percent or even less. - But even if the case fatality rate of COVID-19 is far lower than that of SARS, that's not reassuring because a highly transmissible disease with low mortality will result in many more cases, and therefore ultimately many more deaths than SARS. - Even with a one percent case fatality rate, we hit 3 million deaths in one year because the virus spreads easily. --> As a result, there are so many total cases

Coronavirus

A family of enveloped, non-segmented (+) sense single-stranded RNA viruses of vertebrates - Are a large group of RNA viruses that have a host-derived envelope studied with spike proteins that are used for attachment to host cells. -The genome is not segmented, so it's just one long piece of positive-strand RNA and it has a helical capsid formed by a nucleocapsid protein that associates with the RNA inside the envelope. - The genome is translated upon entry into the host cell The average genome size of the virus is between 27 and 32,000 nucleotides, so they actually contain the largest known genomes among RNA viruses. Different strains utilize different host receptors to attach to host cells. - Different strains infect different animals, different tissues, and different cell types depending on their receptor usage. The viral spike protein is what binds to the host receptor and that initiates endocytosis of the virion into the host cell. - The viral genome then escapes the endosome, much like how influenza's genome escapes the endosome. - Now, the sense RNA genome then undergoes translation to synthesize key proteins, including the RNA-dependent RNA polymerase, which is labeled here as a replicase. --> The replicase then generates minus strands RNA, the complement of the genome, which then serves as a template to synthesize new plus-strand RNA genomes, so for genome replication, and it's also used as a template for producing messenger RNAs that can then be translated to produce viral proteins. - Assembly and exit happen quite differently for the viruses because the virions are actually synthesized and assembled within double-membrane vesicles that form in the host cell cytoplasm and we know that these vesicles are derived from the endoplasmic reticulum, and they're often called virus factories. --> Now, these viral factories transfer completed virions to the Golgi, which then packages them up and secretes them to the cell surface where they are then released by exocytosis. There's still a lot of active research going on to understand how all of these different RNAs of different sizes are synthesized from a single template, and there's also active research trying to understand how this double-membrane vesicle actually forms in its traffic throughout the cell. These viruses are not new and they've been around for a very long time. -The current classification of the virus recognizes 49 species in the family Coronaviridae and within each species, there are numerous strains, so thousands of unique coronaviruses have been sequenced and classified. - These various coronaviruses are widespread among birds and mammals, with bats being host to the largest variety of different coronaviruses. There are seven coronaviruses that are known to infect humans. - Four are coronaviruses that cause the common cold. --> They've been known to be circulating in humans since the 1960s and they've been linked to as much as one third of upper respiratory tract infections during winter outbreaks, so it's pretty likely that you've been infected with the coronavirus at some point in your life. - Three are headline-grabbing coronaviruses that cause more severe disease in humans. --> First was SARS-CoV, which caused an epidemic in 2003, MERS-CoV emerged in 2012, and then finally SARS-CoV-2 is the cause of the current pandemic.

Antigenic Shift

An abrupt major change that results from reassortment of different alleles, creating totally new combinations or new subtypes Can happen with influenza virus because influenza has a segmented genome. - So having a segmented genome is key for shift to happen. Pigs are these mixing bowls because they can become infected with both human and avian flu strains. - If one pig is simultaneously infected with both an avian and a human flu strain, then a cell in that pig can end up with RNA segments from the avian flu strain and RNA segments from the human flu strain. --> Now the virus has no way of distinguishing the RNA segments or where they originated from, and so they will randomly be packaged into new virions such that each virion has one of each of the eight segments. --> The result is the production of new virions that have a mix of RNA segments from both original viruses. --> Now we have this entirely new strain of virus that can have new combinations of alleles of each of the genes in the genome. This is particularly scary because it has the potential to very rapidly produce viral strains that are either highly transmissible, cause really severe disease, or potentially both.

Poxviruses

Atypical Group 1 DNA Virus Have a dsDNA genome, but their DNA replication and transcription occur entirely within the cytoplasm of the host cell - They do not enter the nucleus, which means that no host nuclear proteins are available for the virus to use - Cannot rely on host proteins normally found in the nucleus and must instead bring in their own polymerases - The viral genome in this case will encode the proteins that are needed for genomic replication and transcription In addition, these viruses also have to carry a functional RNA polymerase with them so that when they enter their host cell, their genome can be transcribed - A virus like this will enter a host cell and deposit both the dsDNA genome and a functional DNA-dependent RNA polymerase enzyme into the host cytoplasm - Viral RNA polymerase then transcribes early genes, which produce mRNA that can then be translated by host ribosomes, and translation of those early mRNAs produces a DNA-dependent DNA polymerase, as well as some other proteins that are necessary for genome replication - The last genes encode structural proteins that are needed for capsid and envelope formation. Here, we get those structural proteins, as well as more copies of the RNA polymerase that need to be packaged into the new virion. The viral DNA polymerase makes more copies of the DNA genome We've got our capsid proteins and more copies of our RNA polymerase and so now new virions can assemble and the virus can bud out of the host cell and acquire its envelope

Influenza

Baltimore Class V Enveloped Virus The virus that causes the seasonal flu It's a Baltimore Class V virus with a segmented genome - Its genome consists of 8 molecules of anti-sense RNA --> Each individual RNA molecule comes with a copy of RNA-dependent RNA polymerase associated with it --> Upon entry into host cell, each segment can immediately be used as a template to produce mRNA - Theres a nucleocapsid protein that forms a helical capsid around each individual RNA segment- Each piece of RNA has its own helical capsid - Now, all 8 segments come together into a single virion that has a spherical shape, and that shape is determined by a matrix protein called M1, that assembles spontaneously around the RNA segments forming this spherical-shaped virion The virus has a host-derived envelope studded with several viral proteins, including hemagglutinin or HA which plays a critical role during viral entry, neuraminidase or NA which plays a key role during viral exit, and M2 which is an ion channel that's critical for un-coding the genome - There are also some accessory proteins carried with the viruses that are involved in nuclear export, and so the virus is a unique RNA virus that can replicate in the nucleus of host cells There are 8 segments of - strand RNA, each of which is first used as a template to build mRNA - All mRNAs created have a 5-prime cap and a poly-A tail, and those modifications are necessary because influenza infects eukaryotic cells and eukaryotic ribosomes translate mRNAs that have a 5-prime cap and a poly-A tail --> Its important that the viral RNAs can be recognized by host ribosomes in order to be translated - The first 3 segments here code for subunits of the viral RNA dependent RNA polymerase - Segments 4, 5, and 6 code for structural proteins, so HA, NP, and NA - Segments 7 and 8 are unique because these are RNAs that get alternatively spliced (alternative splicing is a mechanism that enables a single mRNA to direct the synthesis of different protein variants with different biological functions) --> These segments get cut up and spliced in different ways to product distinct mRNAs that code for distinct proteins --> Segment 7 codes for both the M1 matrix protein and the M2 ion channel, and then segment 8 codes for the nuclear export proteins Once influenza has attached to a host cell and escapes the endosomes, it can now replicate -But its replication process is quite unique for an RNA virus because it's a rare example of an RNA virus that does actually replicate in the host nucleus There are a few advantages to replicating in the nucleus 1. splicing happens in the nucleus, and by replicating in the nucleus, the mRNAs can be spliced 2. it's a nice protection mechanism - There are Rnases in the cytoplasm of host cells that can degrade rogue RNAs, and so by entering the nucleus, the virsus is protecting itself from cytoplasmic Rnases 3. The mRNAs that are made in the nucleus acquire a 5-prime cap by stealing caps from host mRNAs in the nucleus, and that process is called cap snatching - Stealing a cap from a host mRNA gives the viral mRNAs a binding site for the host cell ribosome, and it means that the host cell mRNAs don't have a 5-prime cap anymore, they've been stolen - The cell will only make influenza proteins and not use any energy to make its own protein - This allows the virus to really take over the host cell The mRNAs that encode the subunits of the RNA-dependent RNA polymerase are going to exit the nucleus and are translated in the cytosol, and then the RNA polymerase that synthesized there reenters the nucleus again in order to be used in the nucleus to associate with copies of the genome to be packaged into new viral particles - The structural proteins, M1, the nuclear export proteins, the nucleocapsid protein, are also translated in the cytoplasm, and the proteins reenter the nucleus for assembly with the genome. - The RNAs that code for the envelope proteins, so for HA and NA, these RNAs leave the nucleus and are bound by a ribosome in the cytoplasm --> These proteins have ER signal sequences that directs the host ribosomes to the endoplasmic reticulum so that the proteins are made and trafficked through the endomembrane system. --> They're translated into the rough ER, they travel to the Golgi, and then they are inserted into the host cell membrane. - The viral nucleic capsids exit the nucleus with the help of the nuclear export proteins, and then the eight segments of RNA assemble at the membrane with the matrix proteins and bud off of the cell, stealing host membrane with it. --> Now since HA and NA proteins were trafficked to the host membrane, they become part of the viral envelope. - Once the virus has bud off, it actually gets stuck to the host cell membrane because the virus is covered in HA proteins and the host cell still has those sialic acid receptors on it, and so HA sticks to those host cell receptors. - In order to release from the host cell, the virus uses its neuraminidase or NA protein, which is a protease that cleaves any host cell receptors that the HA has stuck to in order to release the virions from the host cell Influenza notoriously evolves very rapidly, which is why there are many different strains of influenza. - It's also why people can get the flu more than one time, and it's also a primary reason why the flu vaccine composition must be reviewed and updated each year to keep up with evolving influenza strains.

Adenovirus

Causes a huge range of disease in humans, including cold, sore throat, bronchitis, diarrhea, pink eye, bladder infection, etc. Typical Group 1 DNA Virus - DNA viruses that use host DNA and RNA polymerases Transcription: Host DNA-Dependent RNA Polymerase Replication: Host DNA-Dependent DNA Polymerase Most DNA viruses that infect eukaryotic cells replicate in the host cell nucleus using the host cell DNA and RNA polymerases - Members of the family poxviridae, so the pox viruses, represent a very interesting exception to this rule

RNA Viruses

For all of these viruses, the RNA genome presents an interesting problem Making copies of the genome involves synthesizing RNA from a RNA template, and making mRNA involves synthesizing RNA from an RNA template -Host cells make DNA copies from DNA templates using DNA polymerases and all cells make RNA from DNA templates using a DNA dependent RNA polymerases, but cells do not routinely make RNA from an RNA template All of these viruses have to have a virally encoded RNA polymerase and more specifically, an RNA dependent RNA polymerase, which is an enzyme that can produce RNA from an RNA template -This RNA polymerase manufacturers genomic RNA and mRNA, that can be recognized and translated by the host cell ribosomes --> Its involved in both mRNA production and genome replication --> The other implications of this is that the replication of an RNA virus occurs independent of host proteins found in the nucleus Most of these viruses replicate in the cytoplasm of the host cell

Host Polymerase Advantages

From the standpoint of a virus, there are two major ______________________ to using ___________ polymerases 1. The virus avoids the energetic cost of manufacturing polymerases inside the host - The reproductive potential of a virus is limited by the energy resources of its host cell. If it doesn't have to synthesize polymerases, it can save those resources for making more capsid proteins and making more copies of its genome 2. DNA and RNA polymerases are so central to cell function that the host species is unlikely to evolve a mutant for that resists the virus

Birds

In ______________, sialic acid is linked to galactose through an alpha-2,3 glycosidic linkage

M1

Matrix protein that assembles spontaneously around the 8 RNA segments of the influenza virus, forming this spherical-shaped virion

Antigenic Drift

Mechanism that occurs because viral RNA polymerase is error-prone. -Unlike host polymerases, a viral polymerase has no proofreading ability, and so mutations happen readily. --> Now, every time the genome is replicated, mutations can occur. --> Many of them are silent or have negative effects on the virus's ability to replicate. --> But sometimes nucleotide changes can lead to subtle differences in protein structure and function which can make the flu virus more effective at replicating. - Can lead to new strains that may be able to attach to host cells better or replicate faster or exit host cells better, which can lead to the emergence of a strain that may transmit better in humans or cause more severe disease.

Hemagglutinin

One of the enzymes found on the surface of the Influenza virus - It is responsible for binding the virus to the cell that is being infected - Is critical for viral entry into host cells The protein bind to sialic acid receptors on host cells, and the virus is taken up by receptor mediated endocytosis - Before the virus can be taken up, the HA protein gets cut by a host protease expressed on the host cell surface - This cut releases a hydrophobic piece of the HA protein called a fusion peptide- which is going to be essential later for the virus to escape from the endosome - Now normally endocytic vesicles in eukaryotic cells, also known as endosomes, mature into lysosomes. Lysosomes are these highly acidic compartments that digest and recycle materials that cells take up from their environment. - Once the virus is taken up into an endosome, it has to escape from that endosome before it gets digested and destroyed - During the normal maturation process of an endosome to a lysosome, the endosome is acidified by proton pumps found in the endosome membrane - Protons accumulate inside the endosome, and theres a proton channel on the viral envelope called M2, which allows those protons to pass across the viral envelope, so the pH also drops inside the viral particle- the decrease In pH leads to a conformational change in the HA protein, and that change causes the HA protein to release from the host receptor - Three circular domains of the HA protein bind to the sialic acid receptor --> Those circular domains have changed confirmation in a different space, and they're no longer bound to the host receptor --> This confirmational change also leads to the fusion peptide, the hydrophobic stretch of amino acids, to become exposed and to move and insert into the endosome membrane --> Its called a fusion peptide because interaction between that fusion peptide in the membrane leads to another conformational change in which the entire HA protein collapses and brings the envelope into close proximity with the endosome membrane. So now they're essentially touching and those membranes can then fuse with each other, and the fusion releases the RNA segments and accessory proteins into the host cell cytoplasm - The virus has successfully escaped from the endosome The HA proteins bind to glycoprotein receptors on host respiratory cells that contain galactose and sialic acid, and the arrangement of these groups can vary between different animals -In birds, sialic acid is linked to galactose through an alpha-2,3 glycosidic linkage -In humans, the sialic acid is linked by an alpha-2,6 linkage -Pigs express receptors with both types of linkages Different alleles of the HA gene codes for HA proteins with slightly different affinities for these different receptors, and so avian flu strains have HA alleles that specifically interact with the alpha-2,3 linkage, which is commonly expressed in the upper respiratory tract in birds -Avian flu strains don't readily infect humans because our receptors are primarily alpha-2,6, which is recognized by strains of influenza viruses that have different HA alleles -Pigs have both receptors in their upper respiratory tract, so they can become infected with both avian and human flu strains The varying HA alleles and variations in the sialic acid receptors determines the host tropism of various influenza strains

Neuraminidase

One of the enzymes found on the surface of the Influenza virus. - It promotes the release of progeny viruses from infected cells. - A protease that cleaves any host cell receptors that the HA has stuck to in order to release the virions from the host cell

M2

Proton channel on the viral envelope of the influenza virus, which allows those protons to pass across the viral envelope

DNA Viruses

The genetic material of these viruses resembles the genetic material for heir host cells - As a result, replication for he viral genome and transcription of viral genes occur much like they do in the host cell For most of these viruses, some portion for he viral particle, usually the genome, migrates into the host cell nucleus - Here, viral genes are transcribed by host DNA-dependent RNA polymerase. This is the enzyme that the host cell normally uses for transcription- It reads a DNA template to build RNA - These viruses must enter the host nucleus because that where the host RNA polymerase is located, and they're going to o rely on the host RNA polymerase in order to transcribe their mRNA —> The nucleus also contains the host DNA-dependent DNA polymerase, which synthesizes DNA from a DNA template. This is the enzyme that host cells normally use to replicate their own DNA. The viral genome is replicated by this host DNA polymerase in order to make more copies of the genome to be packaged into new viral particles - ALL viruses use host ribosomes for synthesis of viral proteins Includes Group 1 and Group 2 viruses

Sialic Acid

The influenza virus recognizes _______________ residues of glycoproteins present on cell surfaces

COVID-19 Viral Efficiency Factors

There are a number of explanations for why the case numbers of COVID-19 far surpassed those of SARS. 1. Wuhan, the epicenter of COVID-19, made containment challenging. - As the largest city in central China, Wuhan is a major transport hub and center for industry and commerce. - It's home to the largest train station and the biggest airport and the largest deep water port in central China, and so China's outward travel has more than doubled in the past decade and it's urban population densities have possibly even tripled. - The proximity of people in residential housing and during commute and in work environments in a mega city like Wuhan amplifies person to person transmission. - In the days just before Wuhan was put under lockdown, more than 5 million people had traveled out because of an upcoming spring festival, and that spread COVID-19 to other provinces in China. 2. There are also a number of recorded super spreader events that occurred across the globe early on in the pandemic. - Cruise ships, a mass gathering of religious groups, ski resorts in Italy and Austria, and other super spreader events contributed to this rapid dissemination of the virus across the globe. 3. The transmissibility is higher for COVID-19 than for SARS, so it spreads faster. - Also, SARS was mainly an outbreak propagated within hospitals, whereas COVID-19 is clearly spread through community transmission, so it's more likely that there are a lot of unknown contacts in the community who will subsequently develop an infection, but they're not advised to quarantine early enough 4. The infectious period in clinical spectrum are different - Mild and asymptomatic cases of COVID-19 are common, and so individuals can spread the virus without knowing it. - It also has a longer incubation period, so individuals that are exposed can spread the virus before they know that they have it. --> Isolation was effective for SARS because peak viral shedding occurred after patients were already quite ill with respiratory symptoms, and so they could be easily identified. --> In contrast, SARS-CoV-2 can be transmitted from asymptomatic or mildly symptomatic individuals, and so waiting until a person is sick to isolate them is simply too late

Influenza Nomenclature

There are different versions of the influenza virus that are named based on a variety of identifying characteristics 1. Virus type - There are four distinct types of influenza viruses: A, B, C, and D - A: Only type that causes worldwide flu pandemics in humans 2. Geographical origin and strain number and the year it was isolated 3. Influenza A viruses are further divided into subtypes based on the different alleles of the two surface proteins: hemagglutinin and neuraminidase - There are 18 different hemagglutinin subtypes or alleles that have been discovered, and 11 different alleles of neuraminidase that has been discovered - A given strain can have any 1 of the 18 HA alleles and any one of the 11 NA alleles - Ex: H3N2 is a way of denoting that a specific viral strain has allele number 3 of HA and allele number 2 of NA

Herpesviruses

These include herpes simplex virus type 1, which causes oral herpes, herpes simplex virus 2, which causes genital herpes, and also varicella-zoster virus, which causes chickenpox and shingles Typical Group 1 DNA Virus - DNA viruses that use host DNA and RNA polymerases Transcription: Host DNA-Dependent RNA Polymerase Replication: Host DNA-Dependent DNA Polymerase Most DNA viruses that infect eukaryotic cells replicate in the host cell nucleus using the host cell DNA and RNA polymerases - Members of the family poxviridae, so the pox viruses, represent a very interesting exception to this rule