Week 3 Virology Lecture Notes (Lecture 7 and 8)
Week 3 Virology Lecture Notes (Lecture 7 and 8) BIOL 123 001
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BIOL 123 001
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This 8 page Class Notes was uploaded by Anastassia Erudaitius on Wednesday April 13, 2016. The Class Notes belongs to BIOL 123 001 at University of California Riverside taught by Dr. Rao in Spring 2016. Since its upload, it has received 27 views. For similar materials see Virology in Biology at University of California Riverside.
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Date Created: 04/13/16
4/11/2016 Bio 123 – Comparative Virology Lecture 7 – Influenza Virus Epidemiology o Seasonal flu: 250,000 to 500,000 deaths This happens because of predisposed conditions like having HIV o In the U.S. we have been infected with flu but we don’t commonly die of flu we have healthier immune systems and can easily fight the flu Spanish flu o Why did they call it the Spanish flu? it was first recorded in Spain (but also occurring in America around the same time) 1918 there was no vaccine death rates peaked Life expectancy dropped because of this flu During 1918 more people died from the flu rather than from WWI o In October you see a huge raise in the death rate flu peaked in October o U vs W curve popular curve U curve (red curve: 1911-1917) death rates only occurred for older people 65+ W curve (blue curve: 1918) 25-34 year olds dying o Life expectancy dropped significantly in October Once you get infected your immunity is going to weaken a little bit at this point you are susceptible to other bacterial infections when people get the flu if they don’t take care of themselves they often get pneumonia o Therefore when people get the flu physicians give them antibiotics to prevent secondary infections o Antibiotics only attack bacteria! NOT viruses When clinics/hospitals have a vaccine available they primarily give them to older people, children, people with diabetes people who are more susceptible 1 Immune system weakens as you get older Viruses CAN cross kingdoms! Not ALL viruses can, but some can o Plant viruses cannot cross kingdoms so a plant virus cannot infect a human Sanitation is extremely important Anthrax, flu, or Sars symptoms are very similar this complicates diagnosis o This is why diagnosis based on symptoms should never be used! Influenza A infection o By 4 days the virus can accumulate to a very high level and can be diagnosed/detected very easily o Transmitted via droplets (coughing, sneezing) and enters respiratory tract o Entry: Influenza viruses enter through the nose and binds to the cilia o Immunity: once you get inflected with influenza you will develop antibodies In one week your body makes antibodies and prevents any new infections from happening N (neuraminidase) and H (hemagglutinin) antibodies produced H neutralizes the virus N does NOT neutralize the virus it reduces the release of the virus from infected cells if the virus cannot be released from infected cells the virus cannot spread This is where the term H1N1 comes from A person may have the flu and get the flu again in later years this is because they are getting infected by a different strain If a person has been infected in the past couple years and is infected by a very similar strain their antibodies may be able to fight the virus A few years ago a completely new influenza strain developed o When the virus binds to the cilia, the cilia are destroyed The cilia protects, it prevents dust and other particles from entering the lungs 2 If the cilia dies it can no longer prevent particles and bacteria from entering the lungs this results in a mucus buildup and a lot of coughing The cilia dies, bacteria enters the lungs, and the person develops a secondary infection o 3 influenza types: A, B, and C all three can infect humans o Infection with one type DOES NOT prevent you from getting another type of influenza strain If you are infected by Influenza A you are protected from multiple strains of A, but you are NOT immune to types B or C o Antigen shift can change from host to host o Influenza can jump from one host to another very easily o In humans it is limited to the respiratory tract In serious cases – the lower respiratory tract o Type A causes widespread epidemics o B causes regional epidemics o C does not cause epidemics o Compared to Poliovirus Poliovirus genome is +ssRNA that means it is messenger sense (it has a cap, and polyA tail) 10-11 proteins encoded in polio RNA but a polyprotein is encoded Influenza has –ssRNA as genome (-) sense is not infectious because they cannot be translated Influenza has 8 different RNAs each encoding different proteins no polyprotein is made each protein is made from a single RNA (DIFFERENT FROM POLIO) Poliovirus has only one capsid protein and there is no outer membrane Influenza has a capsid and an envelope and proteins aromidase and hemagglutinin this structure is totally different from the poliovirus o The virions are long after culturing they become a totally different shape (more spherical) 3 o PB1 and PB2 replicate complex proteins They play a very important role in the life cycle of the virus HA helps sialic acid binding This virus is so different from poliovirus in the replication o Viral replication Enveloped virus has all these glycoproteins in there contains H and N 8 segments of –ssRNA All the viruses that are –ssRNA are the most pathogenic (for all hosts) o 8 –ssRNAs Minus sense is written 3’ 5’ This virus makes a + strand, and then it translated to give you the proteins All 6 minuses make a plus, and each plus makes proteins 7 and 8 make + sense but they produce proteins through a completely different mechanism o Because the endosome results in a pH change it will release the capsid into the host cell o Influenza is an RNA virus but it replicates in the nucleus (UNLIKE poliovirus) o All other RNA viruses replicate in the cytoplasm except influenza o The viruses carry every protein they require o Very unusual mRNA synthesis which you will not find in any other RNA viruses Generally all mRNAs have a cap but this is a ( –) sense RNA How does it make Cap’s for its own RNA? Cap-snatching mechanism – Once it enters the nucleus PB1 and PB2 cleaves the cap from the host’s cellular mRNAs then it uses them as a primer to initiate transcription so when the viral mRNAs are made it will have a cap PA, PB1, and PB2 Now once the RNA has a cap and polyA tail it will exit the nucleus, enter the cytoplasm, and get translated 4 The reason the virus goes to the nucleus is so that it can get the mRNA CAP Antigen drift – any small change happens in the virus Antigen shift – Any large change in the virus can result in a complete change of the virus 5 4/13/2016 Bio 123 – Comparative Virology Lecture 8– Influenza Virus mRNA synthesis and replication of virion RNA o Virus snatches the CAP from the cellular RNA and uses it to prime its own RNA o The virus genome is minus sense so they don’t carry a CAP at all but they need the CAP in order to be translated Types of Influenza RNAs o 2 kinds of +sense RNAs the +vmRNA and the +antigenome RNA o The virus makes 2 kinds of + sense RNAs o One of them is an exact copy of the genome RNA o The + vmRNA has a 3’polyA and 5’CAP because it needs to be translated, so this one is different from the genome RNA Viral mRNAs are not cannibalized for their 5’ Caps o Viruses only tag the cellular mRNAs not the viral mRNAS once the Cap is removed from the cellular mRNAs they cannot translate which means the cell cannot make proteins so now the cell is weak From one mRNA the virus can make three different proteins (M1, M2, M3) o mRNA makes M1 protein, and then after splicing results in M2 and M3 Virus encodes a protein NS1 Once the pre-mRNAs are made in the cell they get processed and exported to the cytoplasm NS1 prevents the mRNAs from exporting to the cytoplasm by snatching the Cap o NS1 blocks the cellular mRNAs from entering the cytoplasm! Once capped mRNAs are made they go to the cytoplasm, proteins are made and then the proteins assemble on the cell membrane All 8 mRNAs are minus sense and are encased in the virion o All 8 mRNAs needed to make all 8 proteins Release of Influeza Virions 1 o New viruses will not reenter the cell again because they want to attack only new cells o Cleaves sialic acid receptors in order to prevent re-entering a cell For test be able to compare poliovirus with influenza what are the similarities and differences Life Cycle o If a small mutation happens in a certain strain it can re-infect someone who was already infected with that strain o Any animal can get infected with two strains of the same Influenza virus If two strains infect the cell then a lot of switching/ recombination may occur between these two strains each has 8 mRNAs 64 different strains can be generated Timeline o Spanish flu – 1919 Pandemic o When recombinants happen you generate a totally knew recombinant virus this recombinant virus has a new property different from the previous strains the recombinant virus must find an ideal host Example: certain insects carry virus, they don’t affect the insect, but once it infects a human the human is affected China o Humans, chickens, and swine all carry different strains of influenzas all interacting very easy to generate new viruses Most Prevalent in Winter o The virus is best transmitted in lower humidity and colder temperatures most ideal temperature for influenza to spread 1918 Spanish flu: H1N1 o Killed more people in 25 weeks than AIDS killed in 25 years o Killed more people in a year than plagues killed in a century o Shows how severe this flu was 9 there were no vaccines in these times Why so Deadly? o Wanted to see what kind of influenza strain killed these people 2 o Found that in 1918 it was an avian (bird) strain, not the swine flu strain 2007 – Kawaoka o Experimented in BSL-4 because it is a highly contagious virus o Generates a lot of cytokines in the body very serious type of flu 1957 Asian flu o First detected in China by June it spread to the U.S. 1968 – Hong Kong Flu o Travels very quickly between countries 2009 H1N1 Swine Flu o We haven’t seen any epidemics by influenza after 1918, until H1N1 Swine flu came because we didn’t have a vaccine for it o Only the younger generations got infected with this because older generations have been exposed to more influenza strains and thus have more antibodies younger generations were more susceptible because they didn’t have enough antibodies Because viruses spread so fast you need the vaccine as quickly as possible H5N1 o Isolated and identified as avian strain it jumped from birds to humans Drugs can prevent attaching of virus, or prevent replication of virus [Note: **plant viruses are host specific! They cannot transfer to humans!] 3
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