Virology: Epidemiology of Infectious Diseases PDF

DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well LECTURE 7: Epidemiology ​ Epidemiology: study of how disease affect communities ○​ Objectives: determine distribution, cause, control and prevention of disease...

DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well LECTURE 7: Epidemiology ​ Epidemiology: study of how disease affect communities ○​ Objectives: determine distribution, cause, control and prevention of diseases in populations ​ Endemic: diseases that persist at a moderate or steady state level within a given geographic area ​ Epidemic: unusually high number of cases in excess of the normal expectation of a similar illness in a population, community or region ​ Pandemic: worldwide epidemic ​ Morbidity: illness or disease state ​ Mortality: deaths caused by a disease ​ Case definition: standard set of criteria used to identify who has a particular disease ​ Incidence: measurement of morbidity; the number of newly diagnosed cases of a disease that occurs in a specified period of time in a susceptible population ​ Prevalence: measurement of morbidity; number of cases existing in a population at a specified time ​ Incubation period: time between infection with a virus and onset of symptoms ○​ Influenza: 1-3 days ○​ Ebola: 2-21 days ○​ Zika: 3-12 days ​ Mode of transmission: how an infectious disease is spread or passed (direct or indirect) ​ Communicable period: time period when infected individual or animal is contagious and can directly or indirectly transmit to/infect another person, animal or arthropod ​ Etiological agent: the pathogen; diseases-causing agent ​ Zoonosis: any infection or infectious diseases transmissible from animals to humans ​ Reservoir: where the etiological agent lives, grows and multiplies (ex: human, animal or arthropod) ​ Pathogenicity: the ability of an infectious agent to cause disease ​ Virulence: measure of severity of disease caused by a pathogen Edward Jenner: ​ Observed milkmaids not badly scarred and disfigured from smallpox ​ Deduced that lesions on milkmaid hands was from cowpox, which protects them from smallpox ​ Performed “experiment” on 8 year old “volunteer” ​ Allan Watt Downie and Variolae (smallpox) vaccine now Orthopoxvirus John Snow ​ Believed in germ theory of disease ​ Cholera epidemic in London, September 1854: ○​ Mapped locations of water intake and sick people ○​ Observed sick individuals that drank from the same water source which was contaminated with Vibrio cholerae ○​ Efforts led to removal of Broad Street pump & immediate and measurable reduction in number of cholera deaths DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well ​ cases of cholera occurred clustered around a water pump on Broad Street- contaminated pump Florence Nightingale ​ Credited with establishment of modern nursing practices ​ Collected statistics & mapped mortality rates of British Army soldiers during Crimean War 1855 ​ Observed many soldiers died from infection from unsanitary hospital conditions ​ Her efforts led to hospital reform and dramatically reduced mortality rates Modes of Transmission ​ Direct: virus passed from person to person through direct physical contact; through contaminated hands, sexual contact, kissing, saliva, other secretions ​ Indirect: virus transferred or carries by an intermediate to a host; by air, vector (bite), ingestion, vehicle (fomites) ○​ Fomites: inanimate objects- contaminated surfaces that require direct contact for transmission (e.g., doorknobs) ○​ Vehicles: non-living- mediums that can spread infection to many individuals at once (e.g., contaminated water causing a cholera outbreak) Chain of Infection ​ Viral pathogen: leaves source through portal of exit→ spreads by 1 or more modes of transmission→ enters body of susceptible host through portal of entry ​ Various ways to break chain of infection at each step: ○​ Rapid pathogen identification ○​ Disinfection and sterilization of fomites ○​ Barrier techniques (face mask and gown) ○​ Proper trash and waste dispersal Herd immunity: ​ If majority of population is protected from disease through immunization/genetic resistance, the changes of major epidemic is highly unlikely ○​ Salk suggested that herd immunity at 85% is sufficient to prevent polio epidemic ​ Development of epidemic in population lacking herd immunity (if only at 32%, epidemic is likely) DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well ​ Vaccination coverage, early diagnosis and rapid public health response are key Surveillance and Serological Epidemiology ​ Surveillance can take several forms: ○​ Monitoring data from mandated reports (morbidity and mortality statistics) ○​ Active field surveillance ○​ Serological screening of population (antibodies represent “footprints” of disease, exposure to disease and protection against disease ○​ Waste water surveillance: SARS-CoV-2 shed in stool→ stool in household wastewater is treated at facility→ facilities sample wastewater and tested for SARS→ + wastewater samples are reported→wastewater is treated and disinfected Tracking Diseases from Outer Space ​ Environmental factors play a role in outbreaks of viral illness ​ Remote sensing and early warning systems ○​ Ex: mosquito survival and behavior influence by temperature and precipitation (they like warm, dry weather and standing bodies of water) — DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well ​ Quarantine: segregation from general population of healthy persons who are not ill but have been exposed to an individual who suffers from communicable disease ○​ Been used through history; efforts involve the cooperation of several health and gov. Organizations ​ Isolation: separation of ill/infected and contagious individuals from healthy individuals ○​ Placards posted on entrances of homes of infected individuals to alert public — Flattening the Curve ​ Refers to curve of # of cases over time ​ Related to the capacity of health systems to treat patients which has a direct effect on overall patient mortality Travel Medicine ​ Before travelling, consider infectious diseases, vaccines, insects ​ High risk tracker categories: immunocompromised, pre existing medical conditions, pregnant women LECTURE 8: Laboratory Diagnosis of Viral Diseases ​ Determine which viruses are causing a particular syndrome ​ Developed because: ○​ patient management ○​ ability of some antivirals ○​ rapid advancement in drug therapies requires proper diagnosis ○​ screening blood supply from donors ○​ tracking novel viral strains ○​ initiating diseases-specific control measures ○​ surveillance (90% of viral diseases unknown) Proving causation of viral diseases ​ Challenges with viral diseases: asymptomatic carrier state & inability to propagate some viruses in cell culture (can’t get lab conditions right) ​ Koch's Postulates- for bacterial pathogen 1.​ Associated with diseases, not healthy host, must be found in all cases of diseased and absent from healthy a.​ Some people are asymptomatic DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well 2.​ Must be isolated from diseases host and grown in pure culture a.​ DIFFICULT to get conditions right 3. Induce same disease upon inoculation of cultured microbe into healthy host b.​ Unethical to infect someone healthy (human), so use different model like mouse which is not always perfectly accurate 4. Can be re-isolated from inoculated host ​ Thomas Rivers- adapted for viral pathogens 1.​ Isolate virus from diseased hosts 2.​ Cultivation of virus in host cells 3.​ Proof of filterability 4.​ Production of a comparable disease when the cultivated virus is used to infect experimental animal a.​ Still difficult 5.​ Reisolation of same virus from the infected experimental animal 6.​ Detection of specific immune response to virus ​ Fredericks and Relman- nucleic acid level; used biotechnology and PCR to offer updated causation guidelines ○​ PCR→ replicate nucleic acids rapidly = helpful because viruses are mainly nucleic acids 1.​ Nucleic acid sequence of pathogens should be present in all cases of infectious disease 2.​ No pathogen-associated nucleic acid sequences should be present in healthy hosts a.​ Can be problems here too 3.​ Nucleic acid sequences of the pathogen should no longer be detected after resolution of disease 4.​ The nucleic acid sequence copy number that correlates with severity of disease is more likely to be the cause of disease a.​ More virus = more harsh disease 5.​ Clinical features and pathologies observed are consistent with biological properties of the suspected pathogen a.​ Must be able to cause/meet the assumed features b.​ Ex: rabies→ this pathogen better be able to cross the BBB 6.​ Pathogen or its antigens detectable in diseased tissues a.​ Gets diseases→ recovered→ find immune response or part of virus antibodies or virions/part of envelope in lymph tissues 7.​ Sequence based evidence of the pathogen should be reproducible Viral Diagnostic in the Clinical Laboratory ​ >60% of infectious diseases seen by physicians caused by viruses ​ Accurate and rapid detection and diagnosis are key to successful treatment ○​ Helps to know what causes the disease ​ Factors influencing laboratory outcome: ○​ Type(correct type) and quality (not contaminated, etc.) of specimen→ ex: if testing for rabies we want a good quality saliva sample DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well ○​ Transport condition and time→ less time travelled = better condition ​ Approaches: ○​ Microscopy (for viruses, if that b/c viruses are small) ​ Light microscopy: used to observe intracellular inclusions & Immunohistochemistry (detects proteins in tissue; can visualize presence, location and amount) ​ Ex: rabies virus antigen is detected using specific anti-rabies monoclonal or polyclonal antibodies Can see virus particles by staining ​ Electron microscopy: used to observe individual virus particles & immunoelectron microscopy (for binding antibody in place to see the other particles better) Stain of small naked icosahedral virus (poliovirus)- can see virions directly Bar, 100 nm DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well ○​ Viral antigen detection- detect epitope of virus; detection of viral antigen indicates presence of the pathogen ○​ Antibody detection- presence of virus-specific antibodies are indirect measure of viral infection ​ ELISA (enzyme-linked immunosorbent assay): answers if the person has virus;test for antigens or antibodies; inexpensive (96 well plates), technically easy to perform, rapid turnaround ​ To detect viral antigen: add clinical sample to dish/well precoated with virus-specific antibodies→ add enzyme labelled antiviral antibodies to react with viral antigen in the sample→ add the enzyme substrate solution→ color indicated positive reaction ​ To detect patient antibodies (works in the reverse)- if you know the part you want to isolate: add patient serum to dish/well precoated with known viral antigens ​ Add patient serum to dish/well precoated with known viral antigens→ enzyme labelled anti human IgG to react with patient antibodies→ add enzyme substrate solution→ color indicates positive reaction ○​ (live) cell culture (in lab)- 1 monolayer (1 cell thick) ​ Used for growing viruses ​ Cell cultures used for virus isolation and identification DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well ​ Monitored for cytopathic effects (CPEs)- seeing cells with virus getting stressed out ​ CPEs (with light microscopy): visual changes in host cell from viral infections: ○​ Formation of inclusion bodies: subtle intracellular abnormalities & can be indicative of species viruses → inclusion bodies coming out of cell as infected ○​ Rounding of cells (enlarged) ○​ Shrinkage ○​ Increased refractivity- how much light passes through the cell→ more light should pass through ○​ fusion/syncytia formation ○​ Aggregation ○​ Loss of adherence ○​ Cell lysis/death ​ Shell Vial Technique- detection of HSV-1 in the coverslip by immunofluorescence ​ Inoculate (coverslip with) tissue culture monolayer with specimen →centrifuge to enhance infection monolayer AT SLOW SPEED→ incubate for 1-5 days→ stain with antiviral fluorescent monoclonal antibodies→ mount coverslip on slide→ read with fluorescent microscope ​ Rapid diagnosis ​ Detects viral antigens before CPE is present ○​ Nucleic acid detection (PCR)- nucleic acid-amplification tests ​ Detect viral nucleic acids: PCR and RT-PCR ​ Diagnosis ​ Management of patients- monitor viral load Advantages and Disadvantages of methods DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well -Rapid, good for non culturable viruses; expensive and difficult -Rapid, easy, large number of samples; false + -Used to quantify viruses; slow, need skill -Quick, large # of samples; expensive, skills, oversensitive -Machine work, NA to all viruses New options in Viral Diagnostics and Discovery ​ DNA microarrays ○​ Diagnostic, detect agents of bioterror ○​ Detect presence or absence of viral pathogenicity genes (higher # = more virulent) ○​ patient management ○​ vaccine quality control ○​ study of host gene response to viral infection ○​ Can do preparation of probes or preparation of the target the virus will attack ​ Protein arrays: spin off of the DNA chip using arrays of antibodies immobilized on chips ​ Metagenomics: helps to discover new pathogens; sequencing DNA from sample and assemble genome ○​ Collect sample→ extract DNA→ sequence DNA→ analyze Working with Viruses in the Lab DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well ​ Working with cells grown in suspension medium inside a vertical laminar flow hood ○​ Biosafety level II ○​ Air decontamination- protects operator and prevents contamination ○​ Air filtered through HEPA filter- circular air current + pressure out, continuous circulation of clean air and keeps it inside ○​ Removes 99.97% of particles ​ Labs are classified by biosafety level: BSL 1 (no pathogens, minimum containment)--> BSL 4 (maximum containment) ○​ PPE varies by BSL ​ Examining viral infection in cells grown as monolayers in flasks using inverted microscope Common methods used to study viruses in research lab ​ Plaque assays ○​ Every viral sample contains a mixture of infectious and noninfectious viruses ○​ Small portion of virions are actually infectious- only 1/300 polioviruses virions are infectious ○​ Superior method for measuring virus is an infectivity assay ○​ Quantitative assay measuring # of viruses in a prepared virus stock: PFU ○​ Plaque: produced when a virus particle infects a cell, replicates and kills that cell; the newly replicated virus repeatedly infects and kills nearby surrounding cells ​ Can calculate by serial dilution math ​ Plaques are visualized with dyes that stain live cells ​ Live cell- purple ​ Where something died- white ​ ID50 & LD50: describe how a pathogen affects a population ○​ Infectious dose- quantification of how infectious a virus, measures how many virions are needed to INFECT 50% of a given population ○​ Lethal dose- quantification of how lethal a virus is, measures how many virions are needed to KILL 50% of population ​ Tissue culture infectious dose (TCID)50: measures how infectious even if it doesn’t kill the host (uses tissue instead of live animal/human) ○​ Developed before plaque assay and still used for viruses that DO NOT FORM PLAQUES but do produce CPE ○​ Endpoint dilution assay: # of infectious viruses required to cause CPE in 50% of cells infected with virus ​ Do plaques = no killing of host Add 10 fold serial dilution of virus to cells in a well plate (start with dilution & add to a plate with hosts DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well cells) → incubate→ examine cells in each well for CPE→ + means CPEs, - means CPEs ​ Neutralization & hemagglutination inhibition assays: detect & quantify virus and strain specific neutralizing antibodies (type of antiviral antibodies) ○​ Without neutralizing antibodies, CPE and hemagglutination occur ​ stress of cells→ clumping of RBC ​ If a person has antibodies against a virus, they will block hemagglutination, preventing RBC clumping. ○​ Hemagglutination assays also used to quantitate or titer virus stocks in research labs ​ Can check if immune response is good/ if you have antibodies ​ Transformation (focus) assays ​ Interference assays ​ PCR-based methods ​ Detection of viral enzymes LECTURE 9: Polio and Enteroviruses ​ Enteroviruses: small, naked RNA viruses, entero = intestines→ transmitted oral-fecal route ○​ Over 70 distinct human enteroviruses (over 20 recognizable associated infectious diseases) Polio ​ History: ○​ description of poliomyelitis dates to ancient Egypt ○​ outbreaks in northern Europe-when it becomes a concern (labels on doors) ○​ NYC epidemic one of the worst in history- 600 deaths, 27,000 paralyzed ○​ 1949: Enders, Robbins, and Weller successfully cultivate Lansing strain of poliovirus in human tissue ​ Clinical features: ○​ Mouth is portal of entry ○​ Oral-fecal or oral-oral ○​ Infants in diapers most efficient transmitters- changing diapers or children touch everything→ put hands in mouth immediately (great vectors) ○​ Avg incubation period: 6-20 days ○​ May be present in human feces for 3-6 weeks ​ Course of MILD infection- 95% of infections are ASYMPTOMATIC ○​ Asymptomatic person shed virus in feces and are able to transmit to others (feces) ○​ 4-8% cause mild symptoms: malaise (discomfort), GI disturbances, fever, flu-like illness, sore throat ○​ Complete recovery occurs within a week ○​ 1-2% have slightly worse symptoms: minor illness→neck/back/leg stiffness & symptoms persist for 2-10 days before complete recovery ​ MAJOR illness DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well ○​ 75% of individuals infected were younger than 30 ​ U.S. conservative estimates: H1N1 flu deaths ranged from 7,500 to 12,000 ​ Seroprevalence studies: Older people had strong antibody reactions toward H1N1 than younger people, suggesting they had some cross-reacting antibodies from exposure to influenza viruses before 1957 ​ February 1976: Cadets at Fort Dix, NJ came down with the flu; one private died. ​ CDC investigated the outbreak. ​ 4 out of 19 throat washes tested positive for H1N1 influenza A (at the time believed to be a “swine” flu closely related to the 1918 Spanish flu virus). ​ 150 million doses of vaccine were prepared in the United States ​ 46 million doses were administered within a few months DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well ○​ Main thing: mass vaccination campaign ​ Swine flu vaccine was fast-tracked ○​ Congress passed a liability protection bill to protect manufacturers of the vaccine ○​ Early problems of the vaccine: ​ Guillain-Barré syndrome (532 people within 10 weeks) ​ 32 deaths ​ Vaccine campaign was suspended in the late fall of 1976. ○​ U. S. government paid more than $90 million on claims cases H5N1 outbreaks ​ Avian strains continue to plague eastern Asia (human cases of H5N1), also H5N1 in birds and poultry ​ Began in March 2024 among wild birds and poultry in the US. ​ January 2025: 11,065 wild birds reported infected & over 153 million poultry cases ○​ High egg prices ​ New danger in this outbreak ○​ Outbreaks of H5N1 in dairy cows (957 herds) → indicates virus adapting to new mammalian host. ○​ Previous H5N1 transmission was from avian to mammal ONLY, not mammal to mammal ​ Used to be chicken to mammal by direct contact…now is spreading between cows which was never observed before → lead to cow to human and human to human Influenza Treatment ​ Antivirals: ○​ M2 inhibitors: prevent uncoating step → no breakdown of capsid ​ Amantidine (sold as Symmetrel) ​ Rimantidine (sold as Flumadine) ○​ N inhibitors: prevents neuraminidase from cleaving sialic acid during budding→ causes clumping at cell surface reducing the viral spread (can’t leave after budding to new cells) ​ Oseltamivir (sold as Tamiflu, pill form) ​ Zanamivir (sold as Relenza, must be inhaled) ​ Peramivir received Emergency Use Authorization to treated hospitalized patients with a severe case of H1N1 in 200 ​ Treatment must begin within 36 hours of onset of symptoms- this is why it is so transmissible- short incubation time ​ Used prophylactically in chronic care facilities DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well ​ Vaccines: ○​ Most effective way to prevent influenza ○​ Flu vaccination time in the United States: October and November ○​ Vaccine grown in eggs ○​ Inactivated trivalent vaccine (flu shot) ​ Recommendations made based on antigenic analyses of recently isolated influenza viruses, epidemiologic data, and post-vaccination serologic studies in humans ​ Vaccine is a cocktail of 3 virus strains (of biggest concern transmission wise): 2 strains of influenza A & 1 influenza B strain ​ Effectiveness depends on: age of the vaccine recipient, immunocompetence of the recipient & degree of similarity between the viruses in the vaccine and those in circulation ○​ Live attenuated vaccine (LAIV)- Licensed in 2003, only approved for healthy people ages 5–49 years ○​ Target groups for vaccines: Persons aged 50 or older, individuals in chronic care facilities including nursing homes, individuals with pre-existing chronic problems like asthma, other pulmonary or cardiovascular problems & immunosuppression, Children on long-term aspirin therapy, Pregnant women, Healthcare workers, Travelers International influenza Surveillance: In 1946, WHO established influenza surveillance program ​ US sentinel physicians send flu stats to CDC: patient visits for influenza-like illness, age groups, morbidity & mortality stats Will there be another killer flu? Are we preparing?: inevitable, pandemic planning teams at international, national, state & local levels; mass media played vital role communicating to public and healthcare professional during 2009 H1N1 pandemic -​ Were surprised COVID was the next pandemic (SARS) and not influenza Lessons learned from SARS outbreak: -​ Within 6 weeks of its discovery – SARS CoV infected thousands of people in 16 countries around the world -​ Spread quickly by air travel -​ Identification of pandemic strains and rapid response to contain outbreaks are paramount -​ Led to more use of HEPA filter to disinfect air particles -​ Researchers working on a universal vaccine based on the use of the influenza A, M2 protein Robert webster, Influenza expert uses reverse genetics to create pandemic avian flu vaccines -​ Avian influenza strains cannot be grown in embryonated eggs→ Avian strains kill the eggs. -​ Reverse genetics allows experts to grow avian strains in cell cultures -​ Developed by Webster so that rapid avian flu vaccines can be made DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well LECTURE 13: Measles ​ Measles: respiratory diseases caused by measles (rubeola virus) - in lining of lungs (same place as influenza) ​ One of the most contagious diseases ​ Been around for >1000 years ​ Millions of people worldwide get measles each year and thousands die from disease ​ Symptoms generally appear 7-14 days after a person is infected (moderate incubation time) ○​ Typically begins with high fever (up to 104), cough, runny nose (coryza), red water eyes (conjunctivitis) ○​ 2-3 days after symptoms being→ tiny white spots (Koplik spots) may appear inside mouth ○​ 3-5 after symptoms begin→ rash, usually begins as flat red spots on face/hairline and spread to neck, trunk, arms, legs and feet ○​ After a few days fever subsides and rash fades ​ History: ○​ In the 9th century, a Persian doctor – Abu Becr Razi, published one of the first written accounts of measles disease. Razi's book al-Judari wa al-Hasbah (On Smallpox and Measles) was the first book describing smallpox and measles as distinct diseases ○​ Francis Home, a Scottish physician, demonstrated in 1757 that measles is caused by an infectious agent in the blood of patients ○​ In 1912, measles became a nationally notifiable disease in the United States, requiring U.S. healthcare providers and laboratories to report all diagnosed cases. In the first decade of reporting, an average of 6,000 measles-related deaths were reported each year ○​ In the decade before 1963 when a vaccine became available, nearly all children got measles by the time they were 15 years of age. It is estimated 3 to 4 million people in the United States were infected each year. Also each year, among reported cases, an estimated 400 to 500 people died, 48,000 were hospitalized, and 1,000 suffered encephalitis (swelling of the brain- caused by prolonged fever) from measles ​ As common as getting chicken pox ​ Measles virus: ○​ Order Mononegavirales ○​ Paramyxoviridae family ○​ Morbilivirus genus ○​ Enveloped, -ssRNA genome, one segment, encodes 8 proteins (including 6 structural proteins- including RNA pol (L and P proteins- for RNA synthesis and replication) ​ Replication: ○​ The H and Fusion (F) proteins mediate transmission of measles virus into host cells in human respiratory tract DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well ○​ Virus is absorbed into host cell when H proteins bind to the CD46 and CD150 host cellular receptors ​ Binds external cell receptor: CD46 and CD150, H acts similar in measles as in influenza ○​ Once uncoated in the host cell, RNA pol transcribes the viral RNA genome into 6 mRNAs→ translated into 8 viral proteins ○​ Viral RdRp (L+P) binds to encapsidated genomic RNA at the leader region, then sequentially transcribes 6 mRNAs by recognizing transcriptional start and stop signals flanking viral genes ​ L+P are components of vRNA: RdRp ○​ mRNAs are capped and “polyadenylated” by the L protein during synthesis ○​ The C protein is produced by leaky scanning of the P mRNA in an overlapping ORF: AUG of C ORF is 19 nucleotides downstream from that for P ORF ○​ The V protein is produced through RNA editing of the P mRNA: which adds an extra non-template G at position 751, shifts the reading frame, and results in an additional 68-aa C-terminus to the N-terminal sequence of 231-aa shared with P ○​ V and C proteins are non-essential for replication and act to inhibit IFN response ○​ These viral proteins function to formulate new helical nucleocapsids for the synthesis of the positive sense viral complementary RNA (vcRNA) and the progeny vRNA. The nucleocapsid interacts with the matrix protein under the plasma membrane and buds, releasing the virion Simple explanation: 1.​ The H protein binds to receptors, F protein helps the virus fuse with the host cell membrane→enters the cytoplasm. 2.​ The L protein (RNA polymerase) reads the (-) RNA genome & makes mRNA copies of each gene. a.​ The mRNAs are sent to ribosomes for protein production. 3.​ The host cell’s ribosomes translate the viral mRNAs into viral proteins (H, F, N, P, L, and M proteins). DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well a.​ Some proteins help with replication, while others form new virus particles 4.​ The L protein makes a full-length (+) RNA copy which is used to make new (-) RNA genomes for new viruses 5.​ The N protein (Nucleocapsid) wraps around the new RNA genomes. The M protein (Matrix protein) helps assemble virus particles near the cell membrane and is released during budding ​ Measles spread through body from initial site of infection in respiratory epithelia ​ Although transmission of virus initially infects URT, replication of the virus in epithelial cells can spread virus to lymph nodes & further replication in lymphatic system can spread to other organs like lung, liver, skin ​ Measles can be serious: ○​ Children 20 years old more likely to suffer from measles complications ​ Especially dangerous for young children and babies ○​ Common complications: ear infections; diarrhea ○​ Severe complications: Pneumonia; Encephalitis ○​ Long-term complications: Subacute sclerosing panencephalitis (SSPE- progressive neurological disorder of children and young adults that affects the central nervous system (CNS). It is a slow, but persistent, viral infection caused by defective measles virus) ○​ Can cause death! ​ Development of measles vaccine: ○​ In 1954, John F. Enders and Dr. Thomas C. Peebles collected blood samples from several ill students during a measles outbreak in Boston, Massachusetts. They wanted to isolate the measles virus in the student’s blood and create a measles vaccine. They succeeded in isolating measles in 13-year-old David Edmonston’s blood ○​ In 1963, John Enders and colleagues transformed their Edmonston-B strain of measles virus into a vaccine and licensed it in the United States ○​ In 1968, an improved and even weaker measles vaccine, developed by Maurice Hilleman and colleagues, began to be distributed; called the Edmonston-Enders (formerly “Moraten”) strain has been the only measles vaccine used in the United States since 1968 (also live attenuated) ○​ Measles vaccine is usually combined with mumps and rubella (MMR), or combined with mumps, rubella and varicella (MMRV) ​ Varicella is causative agent of chickenpox ​ Could get slight fever after shot ○​ Live attenuated measles vaccine: ​ Most attenuated measles vaccines were developed from the Edmonston strain of measles virus ​ The Edmonston B vaccine was the first licensed measles vaccine but was DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well associated with a high frequency of fever and rash ​ The further attenuated Schwarz and Edmonston-Zagreb vaccines are widely used throughout the world, although the Moraten vaccine is the only measles vaccine used in the United States ​ Also use MV as vaccine vector: insertion of spike gene between P and M ​ Measles virus used as vector to insert other vaccines ​ Eradication efforts: ○​ 1978: CDC set a goal to eliminate measles from the United States by 1982. Although this goal was not met, widespread use of measles vaccine drastically reduced the disease rates ○​ 1981: number of reported measles cases was 80% LES compared with the previous year ​ But 1989 measles outbreaks among vaccinated school-aged children prompted the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP) to recommend a second dose of MMR vaccine for all children. ​ Following widespread implementation of this recommendation and improvements in first-dose MMR vaccine coverage, reported measles cases declined even more ○​ Measles was declared eliminated (absence of continuous disease transmission for greater than 12 months) from the United States in 2000. This was thanks to a highly effective vaccination program in the United States, as well as better measles control in the Americas region ​ Biological feasibility of measles eradication: ○​ Measles virus has no non-human reservoirs ○​ The onset of a rash provides easy diagnosis ○​ Although RNA viruses have high mutation rates, the surface proteins (H and F) of measles virus have retained their antigenic structure across time and space ​ Not a lot of variation across different places ○​ The live-attenuated measles virus vaccines developed decades ago from a single strain remain protective worldwide ​ Measles is still common in many other countries ​ Every year, measles is brought into the United States by unvaccinated travelers (mostly Americans) who get measles while they are in other countries. They can spread measles to other people who are not protected against measles, which sometimes leads to outbreaks. This can occur in communities with unvaccinated people DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well ○​ Strong herd immunity for children but can be brought in by unvaccinated people ​ 2019 HIGHEST reported cases (1282) of measles in US since 1994 and since measles was declared eliminated in 2000 ​ Vaccination is best protection against measles (not all vaccination coverage is the same in all places): ○​ 1 dose of MMR vaccine is 93% effective at protecting against measles ○​ 2 doses of MMR vaccine are 97% effective at protecting against measles ○​ In US, widespread use of measles vaccine→ > 99% reduction in measles cases compared with the prevaccine era ○​ MMR vaccine protects you and people who are unable to be vaccinated because they are too young or have weakened immune systems ​ Herd immunity: protect those around you who can’t get the vaccine ​ Who should get vaccinated: ○​ Children- 1st dose at 12-15 months of age & second dose at 4-6 years old ○​ Students at post-high school educational institutions with no evidence of immunity (shows no antibodies- Igs): 2 doses separated by at least 28 days ○​ Adults born after 1957 with no evidence of immunity- at least 1 dose ○​ International travelers with no evidence of immunity- ​ Infants 6 through 11 months of age: 1 dose ​ Children 12 months of age and older (including teenagers and adults): two doses separated by at least 28 days ○​ Healthcare workers with no evidence of immunity - 2 doses separated by at least 28 days ​ Who should NOT get vaccinated: ○​ Anyone who has ever had a life-threatening allergic reaction to the antibiotic neomycin, or any other component of MMR vaccine ​ Antibiotics scrubbed out of the vaccine- there’s antibiotics used so that vaccine can be created sterilly ○​ Anyone who had a life-threatening allergic reaction to a previous dose of MMR or MMRV vaccine should not get another dose ○​ Some people who are sick at the time the shot is scheduled may be advised to wait until they recover before getting MMR vaccine ○​ Pregnant women should not get MMR vaccine, wait until after giving birth. Women should avoid getting pregnant for 4 weeks after vaccination with MMR vaccine property poliovirus hepatitis influenza measles Nucleic acid +ssRNA +ssRNA –ssRNA -ssRNA Genome 1 RNA molecule 7-8 segments DO TABLE COMPARING DISEASES THERE IS A TABLE WITH POLIO AND INFLUENZA.. ADD MEASLES AND HEPATITIS & put incubation time as well Envelope Not enveloped Yes enveloped Virion packaging Packages only Packages RNA RNA and other protein Translation polyprotein mRNAs/splicing Replication site In cytoplasm In nucleus