Enveloped RNA Viruses PDF

Enveloped RNA Viruses  MODULE REVIEW  Wednesday 2/12- Rhabdo + Filo  Friday 2/14- Paramyxo, +filoviridae Orthomyxo, Bunya, Arena  Monday 2/17- Toga, Flavi, Corona  Wednesday 2/19- Lentivirus...

Enveloped RNA Viruses  MODULE REVIEW  Wednesday 2/12- Rhabdo + Filo  Friday 2/14- Paramyxo, +filoviridae Orthomyxo, Bunya, Arena  Monday 2/17- Toga, Flavi, Corona  Wednesday 2/19- Lentivirus (HIV)  Friday 2/21- Hepatitis Virus  Monday 2/24- CBL Virus (Last Lecture of Module 2)  Wednesday 2/26- Start of Module 3, Basics of Bacteria (Recording)  Thursday 2/27- 2:30 pm Micro Exam WHY SHOULD YOU CARE?  CLASS OBJECTIVES  Be able to differentiate naked & enveloped RNA viruses, and how they differ from DNA viruses in terms of structure, replication, morphology, etc. (ongoing)  Be able to define “negative sense” (& positive sense, & how they differ)  Be able to compare & contrast naked & enveloped RNA viruses  Be able to distinguish which viruses are enveloped RNA viruses and the diseases they cause  Be able to diagnose the enveloped RNA viruses based on signs, symptoms, diagnostic tests  Be able to prescribe appropriate prevention and treatments including available vaccinations & therapeutics  Describe the steps of infection and stages of rhabdoviridae presentation  What are the filoviridae?  Useful website: https://www.amboss.com/us/knowledge/General_virology  Today + Filoviridae Virus Family Rhabdoviridae Paramyxoviridae Arenaviridae Bunyaviridae Orthomyxoviridae RNA Strand ssRNA ssRNA ssRNA ssRNA ssRNA RNA Shape Linear Linear Segmented Segmented Segmented RNA Sense Negative Negative Negative (Ambisense) Negative (Ambisense) Negative Segmented? No No Yes Yes Yes Capsid Shape Helical Helical Helical Helical Helical Important Measles, Mumps, RSV, Hantavirus, Rift Valley Examples Rabies HMPV Lassa Fever Fever Influenza ALL OF THE NEGATIVE SENSE ENVELOPED RNA VIRUSES RHABDOVIRIDAE- RABIES VIRAL LIFE CYCLE- ATTACHMENT & ENTRY  Recognize & Attach & bind to their specific receptors  Enveloped: use surface VAPs  Penetration- Virion moves along host cell surface where it encounters entry receptors (aka co-receptors)  Fusion- Viral envelope fuses with the host cell membrane causing the virus to enter  Uncoating: virions disassembled. Capsid is removed to make viral genome accessible to the cellular transcription & translation *THIS IS A NEGATIVE SENSE example because there is the template, POSITIVE machinery SENSE acts as mRNA and can start making proteins (no good visual examples)  REPLICATION & RNA “NEGATIVE SENSE”  ssRNA Classified according to the polarity of their RNA  Negative-sense strand- viral genomes do not immediately begin transcription. Act as template for synthesis of + strand, then used for protein synthesis  All (−) RNA viruses are enveloped & must encode RNA-dependent RNA polymerases for replication  Prone to mutation ASSEMBLY & RELEASE  Self-assembly of the genome and structural proteins produces the nucleocapsid  Assembly  Progeny viral RNA, early & late proteins, & capsid  Release  Usually budding since they are enveloped  Remember M protein & viral budding? RHABDOVIRIDAE- RABIES DISEASE MECHANISMS  RHABDOVIRUS- RABIES  Incubation: ~1-3 months (sometimes 12 months+)  Depends on location of bite  Moves passively within axoplasm of peripheral nerves  Signs & Symptoms-  Fever  Headache  Increased muscle tone (aka stiff & difficulty moving)  Difficulty in swallowing & hydrophobia (contractions of muscles involved in swallowing) occurs in 20%-50%- triggered by pain associated with swallowing water  Focal & generalized seizures, disorientation, & hallucinations common during neurologic phase  Paralysis (15%-60%) may be only manifestation of rabies & may lead to respiratory failure  DIAGNOSING CONSIDERATIONS  Pathologically- Negri bodies present in tissue  Things to consider:  Did the bite result in a skin break?  Has rabies been reported in the state or region where the bite occurred?  Was the biting animal rabid? Is it available for laboratory diagnosis, or did it escape?  Is the species known commonly to be infected with the virus?  Is the biting animal a dog, cat, or ferret that can be observed? Intracytoplasmic inclusions known as Negri bodies like those seen in this hematoxylin–eosin-stained section (arrows) of brainstem are highly pathognomonic for rabies (original magnification, ×158) RABIES PROGRESSION  RHABDOVIRUS- RABIES  Diagnostic tests-  Fluorescent antibody technique- staining suspect brain impressions with a fluorescent antibody to rabies virus  Prevention-  Vaccinating pets (& wild animals)  Postexposure prophylaxis 1. Local wound treatment (soap + water) 2. Passive administration of antibody- Human rabies immunoglobulin (HRIG) 3. Vaccination  4 doses IM deltoid over 2-week period  Immunosuppressed patients 5 doses  FILOVIRIDAE  Enveloped, single-stranded, negative sense linear RNA viruses  Eventually progresses to disseminated intravascular with helical nucleocapsids (like Rhabdovir.) coagulation, shock, & death  Ebola is considered more lethal than Marburg (~50% mort.)  Treatment: Supportive therapy, pain management, dialysis  Transmission: Both have human-human  Two monoclonal antibody treatments, Inmazeb & Ebanga, are FDA approved for Zaire ebolavirus  Marburg- usually bat infested caves  Ebola- primate & fruit bats  Live-attenuated rVSV-ZEBOV vaccine for Zaire ebolavirus-  Incubation: 2-21 days (~8-10 on avg.) recombinant vesicular stomatitis virus (VSV; harmless in humans)  No vaccine or mAbs for Marburg or Sudan Virus, but some  Signs & Symptoms: Hemorrhagic fever with liver & kidney candidates in the pipeline damage, headache, joint pain, sore throat, vomiting, diarrhea ALSO A SCIENTIST Jean-Jeacques Muyembe, PhD  Field epidemiologist & microbiologist  Mysterious outbreak in 1976, like yellow fever or typhoid  He saw hemorrhaging when he’d go to take blood  Sent samples to hospital in Belgium where white scientists named it Ebola after river in village… he never got credit  https://www.npr.org/sections/g oatsandsoda/2019/11/04/77486 3495/this-congolese-doctor- discovered-ebola-but-never- got-credit-for-it-until-now ALSO A SCIENTIST: IN MEMORIAM https://www.iflscience.com/health-and-medicine/ebola- claims-lives-five-study-co-authors-paper-published/  Sheik Humarr Khan, MD  Mbalu Fonnie, nurse  Alice Kovoma, nurse  Alex Moignoi, nurse  Mohamed Fullah, lab technician ALSO A SCIENTIST: IN MEMORIAM MODULE REVIEW  Friday 2/14- Paramyxo, Orthomyxo, Bunya, Arena  Monday 2/17- Toga, Flavi, Corona  Wednesday 2/19- Lentivirus (HIV)  Friday 2/21- Hepatitis Virus  Monday 2/24- CBL Virus (Last Lecture of Module 2)  Wednesday 2/26- Start of Module 3, Basics of Bacteria (Recording)  Thursday 2/27- 2:30 pm Micro Exam WHY SHOULD YOU CARE? NEGATIVE SENSE ENVELOPED RNA VIRUSES WHY SHOULD YOU CARE? NEGATIVE SENSE ENVELOPED RNA VIRUSES MEASLES WAS CONSIDERED ELIMINATED IN 2001 CLASS OBJECTIVES  Be able to differentiate naked & enveloped RNA viruses, and how they differ from DNA viruses in terms of structure, replication, morphology, etc. (ongoing)  Be able to define “negative sense” (and ambisense)  Describe the importance of segmentation  Be able to compare & contrast naked & enveloped RNA viruses  Be able to distinguish which viruses are enveloped RNA viruses and the diseases they cause  Especially enveloped positive and enveloped negative sense  Be able to diagnose the enveloped RNA viruses based on signs, symptoms, diagnostic tests  Be able to prescribe appropriate prevention and treatments including available vaccinations & therapeutics  Useful website: https://www.amboss.com/us/knowledge/General_virology TEST YOUR KNOWLEDGE #1  Based on what you know about RNA viruses, why would you hypothesize that they are more dangerous than DNA viruses?  RNA viruses generally have very high mutation rates compared to DNA viruses, because viral RNA polymerases lack the proofreading ability of DNA polymerases (Also makes it harder to make vaccines… until now) Schematic diagram of paramyxoviridae PARAMYXOVIRUSES Schematic representation of the transcription, translation, and genome replication of paramyxoviruses in the host cell cytoplasm. IMPORTANT RECEPTORS OF THE FAMILY H is Hemagglutinin, HN is a fusion Hemagluttinin-Neuraminidase We’ll talk about this more with influenza/orthomyxoviruses, but this is an important similarity  PARAMYXOVIRIDAE- MEASLES (AD 910)  Pathognomonic (characteristic of a particular disease) symptoms-  Mucosal eruption (enanthem)  Koplik spots (pic on right) epithelial giant cells with surrounding mononuclear cell infiltrates in the submucous glands  Leukopenia (decreased white blood cells)  Three C’s- cough, coryza (swelling of mucus membrane in nose) & conjunctivitis  Serious- Acute disseminated encephalomyelitis (ADEM; demyelinating autoimmune)  Serious- Subacute sclerosing panencephalitis (SSPE) (7-10 y after, mental impairment, personality changes, myoclonus)  Immunosuppression known as “immune amnesia” following infections, so watch for bacterial, viral, and protozoan infections  Vitamin A deficiency & HIV/AIDS leads to poorer outcome  Treatment: Measles immunoglobulin; SSPE is interferon MEASLES AKA RUBEOLA PREVENTION- LIVE, ATTENUATED MMR VACCINE MEASLES IN POP CULTURE  If we have time… “You” https://www.youtube.com/watch?v=xI9w1wOk-Uc  Also, for funzies: “House” https://www.youtube.com/watch?v=gD2_nAimvdU  MUMPS Very communicable disease with only one serotype, only infects humans Found worldwide & endemic in late winter & early spring Spread via inhalation of large respiratory droplets & person-person contact Contagion period precedes symptoms (7 days prior to symptoms) Virus may cause asymptomatic shedding Often asymptomatic, or sudden onset parotitis that is almost always bilateral & with fever; redness & swelling of parotid duct & other glands CNS involvement ~50% of patients; 10% may exhibit mild meningitis, 5/1000 cases of encephalitis Unvaccinated people, (esp. infants 16,000 deaths  However, doctors don’t often test for it as it is not standardly taught in medical school curriculums. Testing often done in hospitals after usual culprits like Covid & Influenza are ruled out.  No current antivirals or vaccine. Treatment includes URI supportive therapy TEST YOUR KNOWLEDGE #2  What is an arbovirus and give me an example?  Arthropod-borne virus  Togavirus > Alphavirus > Chikungunya OR Eastern Equine Encephalitis  Flavivirus > ZIKA OR West Nile OR Dengue OR Yellow Fever   Capacity to exchange genome segments during co- infection by a process called reassortment  When 2+ viruses infect a single host cell, they can each package genome segments from the other virus into a hybrid virion SEGMENTED  Multiple selection pressures can promote or prevent the emergence of reassortant viruses in the population  Reassortment can increase viral fitness by enabling reassortants to escape immune recognition, but it can also decrease viral fitness by uncoupling essential protein sets that interact optimally when kept together  VIRAL LIFE CYCLE- ATTACHMENT & ENTRY  Recognize & Attach & bind to their specific receptors  Enveloped: use surface VAPs  Penetration- Virion moves along host cell surface where it encounters entry receptors (aka co-receptors)  Fusion- Viral envelope fuses with host cell membrane causing virus to enter  (Remember- Depends on pH: neutral pH= fusion occurs at cell surface, acidic pH= fusion occurs in endosome… aka endocytosis)  Endocytosis: https://www.youtube.com/watch?v=D9OtJ U3F6eQ  Uncoating: virions disassembled. Capsid is removed to make viral genome accessible to the cellular transcription & translation machinery  REPLICATION & RNA “POSITIVE SENSE”  ssRNA Classified according to the polarity of their RNA  Negative-sense strand is used as a template to produce mRNA transcripts before translation  Negative-sense NEED Viral RNA polymerase to be transcribed  Ambisense- each strand has regions of + and - polarity, hence ambisense  Occurs in some arenaviridae and some bunyaviridae ASSEMBLY & RELEASE  Self-assembly of the genome and structural proteins produces the nucleocapsid  Assembly  Progeny viral RNA, early & late proteins, & capsid  Release  Usually budding since they are enveloped  Remember M protein & viral budding?  ARENAVIRIDAE- LASSA FEVER  Zoonotic virus (aka animal-borne)  Lassa hemorrhagic fever  Endemic in West Africa  Spread via multimammate rat usually ingestion or inhalation of virus or contact with infected bodily fluids  Most often diagnosed via ELISA assay (for IgM & IgG antibodies)  Treatment-  Ribavirin (antiviral); Rehydration therapy  BUNYAVIRIDAE  Most varied & numerous of the arboviruses  Hantavirus is the exception (zoonotic transmission)  Large (L), Medium (M) & Small (S) RNA segments, pseudocircular  Most have – sense L & M, and ambisense M & S (depending on virus). Ambisense requires 2 rounds of transcription  BUNYAVIRIDAE- HANTAVIRUS  History of potential rodent exposure, fever & fatigue, shortness of breath  No specific treatment, cure, or vaccine  Severe cases- ICU, intubation, & oxygen therapy  Earlier identified, better outcome  Best way is to prevent rodents & DON’T SWEEP droppings USING ANIMAL CONTROL TO PREVENT INFECTION  Keep food & garbage in covered, rodent-proof containers.  Seal holes & cracks in your home to deter rodent access.  Clear brush & junk away from the foundation of your home.  Do not stir up dust in rodent-infested areas. Instead, wet- mop or sponge the area & treat with disinfectant.  When outdoors, do not disturb rodent burrows or handle rodents.  Stay clear of wild animals.  BUNYAVIRIDAE- RIFT VALLEY FEVER VIRUS  Zoonotic virus & arbovirus  Most commonly seen in domesticated animals in sub-Saharan Africa (cattle, buffalo, sheep, goats, camels, etc.)  Contact with animals, or animal tissue, and bites from mosquitoes  Ocular disease (lesions) sometimes with permanent vision loss, encephalitis, hemorrhagic fever may begin with jaundice and other signs of liver impairment, followed by vomiting blood, bloody stool, or bleeding from gums, skin, nose, and injection sites.  ELISA for IgM & IgG, PCR, blood antigens  Usually mild & self-limiting, sometimes hospitalizations & supportive care TEST YOUR KNOWLEDGE #3  Remember influenza G4 from Module 1? Would it be a good example of an antigenic drift or antigenic shift…. And why?  ORTHOMYXOVIRIDAE- FLU VIRUSES  Repeated epidemics & pandemics  Hemagglutinin- binds virus to host cell (erythrocytes & receptors with sialic acid)  Neuraminidase- removes sialic acid receptors from virus particles which prevents new virus from infecting already infected cell  REPLICATION  Orthomyxoviridae viruses are RNA viruses that replicate in nucleus (other- retrovirus)  Viral machinery of orthomyxo viruses cannot make their own mRNAs  Unlike other RNA viruses, orthomyxovirus replication depends on presence of active host cell DNA  “Cap snatching”- Virus scavenges cap sequences from nascent mRNA generated in nucleus by transcription of host DNA & attaches them to its own mRNA  Cap sequences allow viral mRNA to be transported to cytoplasm, where it is translated by host ribosomes SEGMENTED GENOME ALLOWS FOR REASSORTMENT: ANTIGENIC VARIATION  Antigenic Drift- every 2-3 years.  A/Wisconsin/67/2005 (H3N2)-like virus & A/Hong Kong/4801/2014 (H3N2)  Antigenic Shift- every 10 years.  2009 swine flu- H1N1 with swine, avian, and human genes  INFLUENZA VIRUS TYPES: A, B & C  Unlike other RNA viruses, influenza synthesizes mRNA in the nucleus  Infection is established if neutralizing antibodies aren’t present (so make sure you get your flu shot!) and if it overcomes host’s antiviral interferon response  A- seasonal epidemics in humans  HA & NA  More common, antigenic drift  Serious infections  B- seasonal epidemics in humans  HA & NA  Less common, antigenic drift  Less serious infections, but more dangerous in children  C- mild illness, no epidemics  Antigenically stable NAME GAME  S&S, & DIAGNOSTICS  Reye’s syndrome in children- brain swelling & fatty degeneration of the liver  Associated with influenza virus type B (occasionally A)  Aspirin (acetylsalicylic acid) cofactor in disease  Rapid influenza diagnostic test (RIDT)- rapid antigen test for influenza A & B  Better chance of true positive within 4 days of onset  “Gold-standard”- PCR or viral culture (but not rapid)  TREATMENT  Prevents viral uncoating  Rimantadine  Amantadine  Damages release-Neuraminidase (NA) drugs (inhibitors)  Oseltamivir (oral)  Zanamivir (inhalation)  NA removes sialic acid receptors from virus particles which prevents new virus from infecting already infected cell. NA inhibitors prevent sialic acid removal  PREVENTION  Vaccination prevents complications in children & adults- like myocarditis  Inactivated & live, attenuated, cold- adapted vaccines  Inactivated- IM shot, 60-90% efficacy. CANNOT CAUSE INFLUENZA-LIKE SYMPTOMS  Live, attenuated, cold-adapted- nasal spray  Induces local immune response  Results in low level replication in respiratory epithelial cells https://www.instagram.com/p/C3JO0fkg2ME/ The “missing influenza”  May provide more cross- reactivity than inactivated TEST YOUR KNOWLEDGE #1  How does oseltamivir work?  Neuraminidase inhibitor- NA inhibitors prevent sialic acid removal thus preventing the virions from popping off to infect uninfected nearby cells  MODULE REVIEW  Monday 2/17- Toga, Flavi, Corona  Wednesday 2/19- Lentivirus (HIV)  Friday 2/21- Hepatitis Virus  Monday 2/24- CBL Virus (Last Lecture of Module 2)  Wednesday 2/26- Start of Module 3, Basics of Bacteria (Recording)  Thursday 2/27- 2:30 pm Micro Exam WHY SHOULD YOU CARE? POSITIVE SENSE ENVELOPED RNA VIRUSES WHY SHOULD YOU CARE? CLASS OBJECTIVES  Be able to differentiate naked & enveloped RNA viruses, and how they differ from DNA viruses in terms of structure, replication, morphology, etc. (ongoing)  Be able to define “positive sense”  Be able to compare & contrast naked & enveloped RNA viruses  Be able to distinguish which viruses are enveloped RNA viruses and the diseases they cause  Be able to diagnose the enveloped RNA viruses based on signs, symptoms, diagnostic tests  Be able to prescribe appropriate prevention and treatments including available vaccinations & therapeutics  Useful website: https://www.amboss.com/us/knowledge/General_virology Virus Family Togaviridae Flaviviridae Coronaviridae RNA Strand ssRNA ssRNA ssRNA RNA Shape Linear Linear (can switch to Circular) Linear RNA Sense Positive Positive Positive Capsid Shape Icosahedral Icosahedral Helical SARS-CoV, MERS-CoV, SARS-CoV-2, Important Examples Chikungunya, Rubella Virus Zika, West Nile, Dengue, Yellow Fever (229E, NL63, OC43, HKU1) POSITIVE SENSE ENVELOPED RNA VIRUSES  VIRAL LIFE CYCLE- ATTACHMENT & ENTRY  Recognize & Attach & bind to their specific receptors  Enveloped: use surface VAPs  Penetration- Virion moves along host cell surface where it encounters entry receptors (aka co-receptors)  Fusion- Viral envelope fuses with host cell membrane causing virus to enter  (Remember- Depends on pH: neutral pH= fusion occurs at cell surface, acidic pH= fusion occurs in endosome… aka endocytosis)  Endocytosis:https://www.youtube.com/ watch?v=D9OtJU3F6eQ  Uncoating: virions disassembled. Capsid is removed to make viral genome accessible to *THIS IS A NEGATIVE SENSE example because there is the the cellular transcription & translation template, POSITIVE SENSE acts as mRNA and can start making machinery proteins (no good visual examples)  REPLICATION & RNA “POSITIVE SENSE”  ssRNA Classified according to the polarity of their RNA  Positive-sense strand act as mRNA and are directly translated by cellular ribosome to produce viral proteins Positive-sense viral genomes by themselves (aka “naked” or “alone” or “isolated” are infectious.. ASSEMBLY & RELEASE  Self-assembly of the genome and structural proteins produces the nucleocapsid  Assembly  Progeny viral RNA, early & late proteins, & capsid  Release  Usually budding since they are enveloped  Remember M protein & viral budding? TEST YOUR KNOWLEDGE #1  What’s the difference between naked & enveloped RNA viruses?  Non-enveloped (naked)- relatively stable & resistant to temp. changes, acids, proteases, detergents, & drying  Enveloped (not naked)- more fragile & susceptible to heat, acids, detergents & drying  Entry:  Naked virus:  Endocytosis & then virus is uncoated inside cell (3)  Viropexis (Picorna, papilloma, & polyoma)- attach to cell & “phagocytized”  Enveloped virus:  Membrane fusion: Fuses with host membrane & nucleocapsid is released inside (3’)  Depends on pH: neutral pH= fusion occurs at cell surface, acidic pH= fusion occurs in endosome  MOSQUITO TRANSMISSION  Female mosquitoes acquire arboviruses by taking a blood meal from a viremic vertebrate host  Sufficient viremia must be maintained in vertebrate host to allow acquisition of virus by mosquito  Virus infects epithelial cells of midgut of mosquito, spreads through to circulation, & infects the salivary glands  Virus sets up a persistent infection & replicates to high titers  Salivary glands can then release virus into saliva which is transmitted to human host during feeding TOGAVIRIDAE Family: Togavirus Genus: Genus: Alphavirus Rubivirus Chikungunya* Rubella Eastern Equine Encephalitis* *Arbovirus (Arthropod-Borne Virus= informal name used to refer to any viruses that are transmitted by arthropod vectors.  THE ARBOVIRUS CHIKUNGUNYA  Usually begin 3-7 days after being bitten by infected mosquito  Fever & joint pain*  Headache  Muscle pain  Joint swelling  Rash  Test for IgM & IgG antibodies against CHIKV  IgM highest 3-5 weeks after illness onset, & last ~2 months  No vaccine, prevent mosquito bites  Rest, fluids, NSAIDs for Chikungunya arthritis (once rule out Dengue)  EASTERN EQUINE ENCEPHALITIS VIRUS (EEEV)  Natural host is in birds, spread via mosquitoes, can infect humans & horses  Incubation period ranges from 4 to 10 days  Can result in asymptomatic, febrile illness (fever) or neurologic disease, including meningitis or encephalitis  ~30% of people die & many survivors have ongoing neurologic problems  No vaccine; supportive therapy, PREVENT mosquito bites The Indiana Department of Health (IDOH) considers 13 Northern Indiana counties to be at risk for EEE virus transmission due to the presence of suitable habitat for the vector mosquitoes: Adams, Allen, DeKalb, Elkhart, Kosciusko, LaGrange, Lake, LaPorte, Marshall, Noble, Porter, Steuben, and St. Joseph  RUBELLA- “GERMAN MEASLES” (EXCEPTION TO ARBOVIRUS THEME)  Airborne droplets when people cough & sneeze  DANGEROUS for women in 1st trimester- miscarriages, fetal deaths, stillbirths, Congenital Rubella Syndrome (CRS)  CRS= Severe birth defects; classic triad is cataract, deafness and cardiac malformation  90% chance of giving birth to baby with CRS if infected during first-trimester  25-50% of infected people will not experience symptoms  Adults- usually mild, self-limiting  Low-grade fever, sore throat, rash from face that spreads to body, sometimes pink eye  Children- usually mild. , self-limiting. Red rash is usually first sign. Spreads from face to body.  Low-grade fever, headache, pink eye, swollen lymph nodes, cough, runny nose  Last major rubella epidemic in the US 1964-1965  ~12.5 million people got rubella-11,000 pregnant women lost babies, 2,100 newborns died, & 20,000 babies born with CRS “blueberry muffin” skin lesions Widespread rash- can be less red than traditional measles  No specific treatment, bed rest & fluids. Prevention- Measles, Mumps, Rubella (MMR) vaccine  Vaccine program started in 1969  Eliminated in US in 2004, but we get ~10 cases/year FLAVIVIRIDAE  ZIKA & WEST NILE VIRUSES  ZIKA (ZIKV)  Symptoms- Usually none, but fever, rash, headache, joint pain, conjunctivitis, muscle pain.  Severe consequence- *Microcephaly if infected during pregnancy. Despite a lack of symptoms, virus can be transmitted sexually & vertically to fetus for at least 3 months after infection  Treatment- No specific. No vaccine, yet. Treat secondary symptoms (NSAIDs).  Infection correlates with higher incidence of Guillain-Barré  West Nile  Symptoms- 8/10 no symptoms, 1/5 fever, rash, body aches, joint pain, vomiting/diarrhea  Severe consequence- 1/150 CNS infection w/ encephalitis or meningitis. 1/10 die  Treatment-No specific. No vaccine, yet. Treat secondary symptoms (NSAIDs).  DENGUE  Symptoms-1/4 get sick. Usually 4-6 days after infection. Sudden, high fever, severe headaches, pain behind eyes, severe joint & muscle pain, fatigue, nausea, vomiting, skin rash (2-5 days after fever), mild bleeding  Severe consequences- Dengue Hemorrhagic Fever & Dengue Shock syndrome  Treatment- rest, fluids, Tylenol/acetaminophen NOT NSAIDs b/c they increase bleeding risk & thrombocytopenia  Vaccine: Dengvaxia (specific for patients w/ previous infection)  YELLOW FEVER  Symptoms- occur 3-6 days after infection. Fever, chills, headache, backache, and muscle aches  Severe consequence- ~15% get serious illness that leads to bleeding, shock, organ failure  Complications during toxic phase of yellow fever infection include kidney & liver failure, jaundice, delirium, coma, & death  Treatment- No specific treatment. Supportive therapy, rest, & fluids (no acetaminophen or ibuprofen as this increases risk of bleeding)  Yellow Fever Vaccine- signed & stamped International Certificate of Vaccination of Prophylaxis (ICVO aka “yellow card”) https://www.youtube.com/watch?v=X9fLbfzCqWw TEST YOUR KNOWLEDGE #2  You are a physician working in an emergency room in Africa and you encounter a 23-year-old biologically male patient who is an American medical student from MU-COM volunteering with a medical mission group. He is complaining of sudden, high fever, joint pain, severe headache, and fatigue. A history reveals that he has been outside without wearing Deet as much as he should have been. He is able to present you with his stamped International Certificate of Vaccination of Prophylaxis.You draw some blood to run some rapid antibody tests, however none are conclusive for anything. 1. Why were the antibody tests inconclusive? 2. What test should you follow up with? 3. What medication should you give him for joint pain & aches while you wait for more conclusive results (and why)?  WHY WAS IT INCORRECT WHEN PEOPLE WERE REFERRING TO SARS-COV-2 AS "THE CORONAVIRUS"?  First identified in 1960s, named for the solar corona–like appearance (surface projections) of their virions  Causes ~30-35% of “common cold” (2nd behind rhinovirus)  Strains that cause “common cold”- 229E, NL63, OC43, HKU1  Can also cause gastroenteritis & pink eye  CORONAVIRIDAE  Serious respiratory infection: Severe Acute Respiratory Syndrome (SARS-CoV, 2002), Middle Eastern Respiratory Virus (MERS-CoV, 2012), Coronavirus Disease 2019 (SARS-CoV-2)  Signs & Symptoms: https://www.youtube.com/watch?v=OOJqHPfG7pA  Serious symptoms:  Cytokine storm https://jamanetwork.com/journals/jamainternalmedicine/fullarticl e/2767939  Acute respiratory distress syndrome (ARDS): fluid builds up in the air sacs (alveoli) in your lungs which keeps your lungs from filling with enough air, which means less oxygen reaches your bloodstream. This deprives your organs of the oxygen they need to function ANTIGENIC DRIFT & COVID  Why are there so many mutants? https://www.youtube.com/watch?v=Ha6yUxze1vk  Phylogenetic tree: Https://nextstrain.org/ncov/ COVID-19 PREVENTION  mRNA Vaccine!!!  Pfizer & Moderna  https://www.youtube.com/watc h?v=7DlcRSvuvnw  J&J vaccine (adenoviral vector vaccine)  No longer offered in US. EUA expired May 2023  https://www.youtube.com/watc h?v=zcUXWbtBQHQ  Novavax- protein subunit vaccine more “traditional”  COVID-19 TREATMENT  Passive immunization  Regen-CoV (monoclonal antibody)0https://www.youtube.com/watch?v=Ye78-qa5pXA  Antivirals 1. Remdesivir (Veklury)  Nucleoside analogue  Speeds up recovery. IV delivery, expensive, & hard to manufacture  Only FDA APPROVED drug to treat covid 2. Ritonavir-Boosted Nirmatrelvir (Paxlovid) 3. Molnupiravir (Lagevrio)- prodrug of broadly active, ribonucleoside analog; causes hypermutations in RNA ALSO A SCIENTIST Jessica Malaty-Rivera, MS  Egyptian-American.  Microbiologist | Infodemiology enthusiast | Science Communicator | Vaccine Advocate | Public Health Nerd  I spend my days tracking and writing about emerging infectious disease outbreaks, vaccines, science misinformation, and healthcare innovations.  I tweet, talk, and write in English, Arabic, and Spanish.  SciComm Lead @COVID19Tracking  @jessicamalaty Twitter, @jessicamalatyrivera IG ALSO A SCIENTIST Dr. Alyssa Fears, MPH&TM, Master of Public Health & Tropical Medicine- Disaster Management  PhD Tulane University School of Medicine, Biomedical Science Program  Aerosol generation and exposure of infectious material to non- human primates and mice. Select Agent and Tier 1 Select Agent work in Biosafety Level 2 and Biosafety Level 3 conditions.