Q3 Microbiology Viruses

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Hepatitis E

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Calcivirus Family: +RNA, non-enveloped. Fecal-oral transmission- mostly water infection. Acute hepatitis, does not become chronic. Not in US (typically Asia, Africa)



Norwalk/Norovirus
Fecal-oral transmission
Responsible for 50% of non-bacterial gastroenteritis
Symptoms: nausea, diarrhea, abdominal cramps, fever, headache (D/T fluid loss)
Eat bad food/water→grows in gut epithelium→nausea→vomiting→diarrhea→resolves in 1-3 days
200,000 cases/year in US
More common in confined areas: cruise ships, summer camps, military, nursing homes, schools
Food/water supply contaminated, ice machines in hotels contaminated

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Norwalk/Norovirus

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Calcivirus family: Norwalk/Norovirus
Fecal-oral transmission
Responsible for 50% of non-bacterial gastroenteritis
Symptoms: nausea, diarrhea, abdominal cramps, fever, headache (D/T fluid loss)
Eat bad food/water→grows in gut epithelium→nausea→vomiting→diarrhea→resolves in 1-3 days
200,000 cases/year in US
More common in confined areas: cruise ships, summer camps, military, nursing homes, schools
Food/water supply contaminated, ice machines in hotels contaminated

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Hepatitis C

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Flavivirus Family. Hepatitis C- humans and chimpanzees only
Blood-blood transmission
Chronic hepatitis- hides well from immune system- can be a carrier
Worldwide: 300 million carriers
US: 3 million carriers (1% of population are carriers)
Africa: 10% of population are carriers
Symptoms (6 months after infected): jaundice, dark urine, GI pain, nausea
85% of infected→ chronic and show symptoms
Risk groups: IV drug use (60% of cases), sexual (20% of cases) occupational (needle prick), blood contact (tattoo, toothbrush, razor)
Blood transfusion used to be a risk factor, but screening is VERY effective!
Mother→child; during birth- 6% chance
Mortality: 1-5%
5% develop hepatocellular carcinoma
Liver cells are constantly undergoing division→ greater chance for a mistake due to a mutation→ cell becomes cancerous
#1 cause of liver transplants in US!
Take liver out, put new liver in→ new liver will still get infected
Treatments:
Interferon (α/β)- 40-50% effective- CURES!
Ribavirin- nucleotide analog
Looks like a “G” (G,A,T,C)- can base pair with either a “C” or a “U”
Causes virus to overmutate: virus still replicates, but progeny are useless

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• HEPATITIS a

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HEPATITIS A (Infectious Hepatitis ( “viral hepatitis”)

(+RNA, naked →non-enveloped)
• Causes acute infection of liver by attacking hepatocytes they have receptor for HepA
• 30,000 cases/yr U.S.A.
• Symptoms
• Flu like fever (sudden), GI and abdominal pain, nausea and vomiting, diarrhea, and once in the liver →jaundice, dark urine
• Children→>90% asymptomatic to minor symptoms Adults→25-50% asymp 0.3% fatal if symptomatic
• Recover→should be no permanent damage, liver heals, you do NOT carry virus!
• Transmission
• Fecal Oral via day cares, shellfish, sushi, children →(daycares, crowded housing, pools) poor sanitation – 10^7viruses/gram feces
o Survives stomach pH, high temps, detergents, saltwater & shellfish
• Grows in GI (slowly over 30 days)
• Asymptomatic shedding via stools
• Moves to Portal Blood
• Moves to Liver
• Damages Hepatocytes in attempt to eliminate the virus

• Incubation 4 weeks (shedding 2wks prior to SXs) no SXs at 1st b/c no damage yet
• Treatment→ Vaccine in Pill form containing killed virus does NOT mutate

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rhinovirus

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Picornavirus (NOT Enterovirus)
+RNA, Naked 34*
Most common viral infection
Common Cold (70%) → different from flu!!
Has over 100 serotypes→ this is why people are re-infected every year (you would need memory for every serotype to not be infected)
• 62 million cases/yr U.S.A
• Defense (immune response IgA is most important)
• Interferon system
• Innate response
o If it is not strong enough to kill it then you will not form memory because you will not be infected with the virus
• Replication→Impossible at 37'C so it remains in the upper respiratory tract (it cannot survive in the lower RT because the temperature is too warm)
• Temperature and pH sensitive
o - cant invade stomach (acid)
o - grows in nose (lower temp)
o - grows in upper resp. tract
o - can invade thru eyes

• Seasonal: Winter (because its colder and people are gathered in one area) → inc. risk of spreading the infection

• Symptoms
• 90% infected show symptoms - Nasal discharge, sneezing, sore throat, fatigue (overall upper respiratory)
o (via histamine and bradykinin release)
• Incubation: 2-3 days → symptoms last days to weeks
• Spread: by aerosols and fomites (especially fingers)
• Secondary infections → Haemophilus influenza, Strep pneumonia
• Note: Corona virus also presents with “cold symptoms”.

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coronavirus family (general characteristics)

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• Large number of genes (30,000 nucleotides)
• Members Include:
• Coronavirus
• SARS (Sever Acute Respiratory Syndrome)
• +Sense RNA, Enveloped
• Has a protein cap
• When a ribosome binds to a cap it is now looking for an AUG
• In this case because it jumps an AUG may be missing there will be a gap so it must too jump down to the next AUG to make another protein allowing them to be different
• Coronavirus actually makes individual RNAs for their protein (only make 4 proteins)

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Coronavirus Coronavirus

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• CORONAVIRUS
o +Sense RNA, Enveloped with protein cap
o Common cold (30% caused by this)
• 2nd most common cause
• More powerful cold than rhinovirus (kind of between cold and flu)
o Upper respiratory tract only (can grow at 37C)
o Infects ciliated epithelium – destroys epithelium creating a persistent cough and sore throat
o Tissue specific unlike rhinovirus
o Same symptoms as rhinovirus
• Fever, nasal discharge,cough, sneezing, sore throat, fatigue (overall upper respiratory)

o Seasonal mostly in winter
o Only transmitted between humans
• Defense
o Interferon system

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SARS

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coronavirus family
o +Sense RNA, Enveloped with protein cap
o Upper and Lower Respiratory infection
• Severe Atypical Pneumonia
• 10% fatality
• High fever, atypical pneumonia, malaise, headache, body aches
• Respiratory distress
• (10-20% of those infected have to go on mechanical ventilation) -> death
o First reported in Asia in 2003, 8100 cases, 774 deaths
o NO cases since 2004 BUT it can happen again
o Spread →Airborne droplets - via aerosol - very easily → person-person
o Incubation→3 days
o Defense
• Seems to inhibit interferon response and has faster access to the tissue getting deeper

• Replication
o Does not reveal to the outside world that the cell is infected →builds a virus inside the cell → send it to the nuclease → puts a second membrane around it (hiding the antigens) → fuse to plasma membrane → exocytosis - (immune system --NK doesn’t kill the cell because can’t recognize the virus)
• Mutation frequency: (how many mistakes per replication?) Normally→ 1 mistake/10 billion (each cell of genome =3 billion nucleotide) → 1 mistake/ 3 cell replication
• SAR→will make 3 mistakes per genome. When replicating - 1/10,000 nucleotides mistakes (same level as HIV)
• This is even without selected pressure- therefore /c drug pressuring this could increase!
• This is a big advantage because they can rapidly evolve!!!!!
• This is also a disadvantage because a lot of the viruses that come out with be useless and dead - but at least half of them will live.

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PICORNAVIRUS (family)

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• Single stranded +Sense RNA – no envelope
• Members in this family are:
o Enteroviruses
• Polio, Coxsackie, Echo
o Rhinovirus
o Hepatitis A

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enterovirus - polio

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• General
• Paralytic poliomyelitis
• Takes 5-10hr to kill cell therefore no time for cell to make interferon, 50,000k progeny/cell
• USA polio free since 1994, Europe since 2002, still in Afganistan, Nigeria, India, Pakistan 2000cases/yr
• In1900-1950, 1% of people paralyzed due to sewage issues
• Survives stomach acid
• Only 3 serotypes – Antigenic variants
• Very stable - little mutations – very careful with replication
• Symptoms
• 90% asymptomatic → infect, replicate, leave through fecal matter
• 10% into blood stream → develop into viremia GI distress, fever, headache) lasts 3-5 days
• 1% enter CNS (develop paralysis)
• Developed countries 3X more chance of paralysis
• Because contract Polio at an older age vs underdeveloped countries
• Exposure post puberty have 3x greater risk to develop paralysis
• Post Polio Effect
• Some neurological damage upon initial exposure, but not felt until 30-40 years after exposure because of older age
• Weakened muscles, fatigue, respiratory problems, joint pain
• Transmission
• Humans only host
• Fecal Oral
o Gets into lymphatic tissues
o Replicates in tonsils & Peyer’s patches
• Replication
• The Polio Proteins will alter the ribosome of the cell so that it will only recognize the virus +sense RNA→This way the virus takes over and uses everything for itself making only virus proteins
• Internal Ribosome Entry Site (IRES)
o On the +Sense, functions to bind the ribosome since there is no cap, the enzyme for polio that cleaves a protein of the ribosome is so that it will halt translation and then the cell’s ribosome is only recognizing IRES on the virus & replicates that
• Treatments→VACCINE
• SALK 1954→Killed Inactivated Vaccine
o 3 serotypes (differed by antigen) all injected
o produce IgM memory – no IgA
• SABIN 1960→Live Attenuated Vaccine
o 3 serotypes, infected rats making it rat adapted virus
o take live virus out of rats give to humans
o advantage→natural infection to induce IgA response
o disadvantage→ virus can mutate back in 24 hours gives immune system head start but now person is carrier and can expose virus to other people

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coxsackie

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picornavirus - enterovirus
2nd most common virus along with echovirus – Stomach flu
• Diarrhea, abdominal cramps, nausea, vomitting
• Myocarditis & Pericarditis – 50% caused by coxsackie virus
• SXS→fever, tachycardia, shortness of breath, chest pain

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echovirus

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picornavirus - enterovirus
• Viral cause of Meningitis
• 90% caused by viral – 1% fatality in children
• Stiff neck, headache, fever, nausea, confusion
• Differentiate between bacterial – spinal tap
o Cloudy culture – bacterial
• Seasonal – summer/fall
• Primarily infects children
• Fecal / oral or oral / oral transmission

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virus -> intracellular obligate parasite

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Obligate Intracellular Parasite→may be viable for hours to days outside of host
• Cannot replicate itself; no energy metabolism
• Needs ribosome from cell to make protein; needs to use cells DNA polymerase to replicate itself
Structure

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virus - structure

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• Very crystalline structure
• Icosahedral Shape (20 Faces) OR Helical Shape of Capsid typically
• Most are icosahedral – 20 equalateral triangles
o Capsid – protein coat that protects the nucleic acid on the inside
o Cary nucleic acid from cell to cell
• Envelope – a lipid bilayer surrounding the capsid; present around some, but NOT all viruses
• Receptor binding proteins
o Viral proteins that bind to receptors on host cell membranes
• Cell Type→most will only infect specific cells
• Ex: flu just targets lung cells; HIV – T helper & macrophages
• Species Type→most are species specific
• Nucleic acid
o DNA or RNA
• Whichever it is, it will always be that
• Ex: Influenza – RNA virus will always be a RNA virus; papilloma – DNA virus
• RNA and DNA can be single or double stranded

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virus - process

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Process
• Virus wants to come in and take over cell and have the cell now work for it to replicate itself 1000 times over
• Virus will follow the rules of the cell to replicate the DNA and RNA using the complement system of replication
• Most viruses enter cell via endocytosis
GOAL→get inside cell to make progeny viruses

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virus - steps of viral invasion

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1. Virus binds to host cell membrane
2. Virus endocytosed into cell
3. Endosome fuses with lysosome
4. pH of endosome changes signaling virus (conformational change)
5. Virus’ membrane fuses with endosome membrane (pH dependent virus fusion)
6. Virus exits the endosome

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virus - genome replication

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GENOME REPLICATION
• Replication by making complement of genetic code
o Example: ACGT → TGCA
• Replication→can have many errors, do not proofread
o UNLIKE Human cells which double check their DNA while they replicate
o Viruses are sloppy they do NOT check their progeny and are not careful
• Viruses replicate quickly and abundantly
• If there are a few mistakes – it does not matter much because there are so many created
• Human cells for replication
o DNA dependent DNA polymerase → DNA to DNA
o DNA dependent RNA polymerase → DNA to RNA
o Viruses can use either of these or both for replication
• Viruses polymerases not contained in our own cells
o RNA dependent RNA polymerase → RNA to RNA
o RNA dependent DNA polymerase → RNA to DNA (Reverse transcriptase)
• RNA→Single (ss) or Double (ds), high chance MUTATION (1/10k)
o POSITIVE SENSE (+) virus
• RNA is just like mRNA (messenger RNA)
• Can immediately translate PROTEINS via host’s ribosomes
• No proofreading
• Ultimately→We are going to make a lot of viral proteins
o NEGATIVE SENSE (-) virus
• CANNOT immediately make viral proteins
• –RNA viral template used to first make +mRNA
• The newly made +mRNA can then make viral proteins
• Virus must bring RNA dependent RNA polymerase (RDRP) with them into cell
o [note: we do not have RDRP!!!!]
o RDRP used to make complimentary (+) stranded mRNA
• DNA→Single (ss) or Double Stranded (ds)
o DNA genome needs DNA dependent DNA polymerase
o Also needs DNA dependent RNA polymerase to make mRNA
• Can be from cell or from virus
o DNA viruses must be transcribed first into mRNA before they can make viral proteins
o Retrovirus
• + sense RNA which creates DNA
• Needs RNA dependent DNA polymerase → reverse transcriptase
• Also needs DNA dependent RNA polymerase from cell