Introduction to Viruses 2024 PDF

AN INTRODUCTION TO VIRUSES Mark Cinquegrani, PharmD, BCACP, AAHIVP (he/him) 11/8/24  Learning Objectives COMPARE AND CONTRAST DESCRIBE PROPERTIES OF RECOGNIZE THE DIFFERENCES VIRUSES WITH OTHER CELL VIRUSES, INCLUDING THEIR BETWEEN DNA AND...

AN INTRODUCTION TO VIRUSES Mark Cinquegrani, PharmD, BCACP, AAHIVP (he/him) 11/8/24  Learning Objectives COMPARE AND CONTRAST DESCRIBE PROPERTIES OF RECOGNIZE THE DIFFERENCES VIRUSES WITH OTHER CELL VIRUSES, INCLUDING THEIR BETWEEN DNA AND RNA FORMS MOLECULAR STRUCTURE, VIRUSES COMPOSITION, AND REPLICATION STRATEGIES VIRUS STRUCTURE Properties of Viruses Can’t copy genetic Obligate material intracellular No energy parasites No “machinery” to synthesize proteins! No Cannot ribosomes carry out Can’t or metabolic generate organelles processes ATP 5 Virus Size Comparative Sizes Diameter Virus 20-300 nm Bacteriophages 10-100 nm Staphylococcus 1000 nm Red blood cells 6000-8000 nm Width of human 100,000 nm hair Virus Shape Capsid: Protein coat that Nucleocapsid: structure covers the genome; composed of the nucleic contains repeating subunits acid genome and the capsid (capsomeres) proteins Capsid Shapes Icosahedral: - Capsomers arranged in triangles - Spherical shape - Can be enveloped or naked Helical: - Capsomers arranged in a hollow-coil - Rod-shaped - Always enveloped Viral Envelopes VIRUS COMPOSITION Lipid Envelopes ◦ Lipid from the host cell membrane is acquired when the viral nucleocapsid exits the cell in a process called “budding” ◦ Viral envelopes contain glycoproteins on the surface ◦ Attach to host cell receptors during viral entry ◦ Presence of an envelope gives the virus instability ◦ More sensitive to heat, drying, detergents, and lipid solvents  Provide Structure Protect the genome Proteins Facilitate transfer and attachment Act as antigens Nucleic Acids o Genetic material is either DNA or RNA o Single or double- stranded, circular or linear, segmented or non-segmented o Positive or negative- stranded o Most are haploid RNA Viruses RNA Virus Polarity Positive (+) Stranded Negative (-) Stranded ◦ Just like messenger RNA ◦ Cannot be immediately (mRNA) translated ◦ After it enters the cell, it can ◦ Needs to first be converted be immediately translated to to positive-stranded by RNA the host’s ribosomes into polymerase protein ◦ Human cells do not have this ◦ Viruses must supply their own RNA polymerase in their capsid DNA Viruses DNA Viruses ◦ DNA cannot be directly translated into proteins ◦ Must be transcribed into mRNA, then translated into structural proteins and enzymes ◦ Most DNA viruses have BOTH a negative (-) and a positive (+) strand ◦ Positive strand read, negative strand ignored  DNA RNA Transcription polymerase mRNA Translation Structural Proteins & Enzymes DNA vs. RNA Viruses: Summary RNA Viruses DNA Viruses ◦ Single-stranded ◦ Double-stranded ◦ Either (+) or (-) stranded ◦ Most show icosahedral ◦ Most show helical symmetry symmetry ◦ Replicate in the cytoplasm ◦ Replicate in the nucleus ◦ Most are enveloped ◦ Tend to be more genetically complex than RNA viruses VIRAL TRANSMISSION AND REPLICATION Viral Transmission Direct Person to person; no fomites Indirect Via inanimate object (fomites) Animal to animal with humans an accidental host Arthropod Vector Viral Transmission By sexual contact: HPV, HBV, HSV, HIV, HCV Direct By mouth to mouth: HSV, EBV By exchange of contaminated blood: HIV, HBV, HCV Indirect Fecal-oral: HAV, enteroviruses, rotaviruses By fomites: Norwalk virus, rhinovirus Animal to Bites (rabies) animal By droplet in rodent-contaminated quarters Arthropod Mosquitos: dengue, yellow fever, West Nile, Zika vector Ticks: Colorado tick fever Viral Replication Attachment Synthesis of Release of Uncoating & viral virions from of genome penetration products host cell BACTERIOPHAGES  Phage Therapy Bacteriophages Imlygic® approved October 27, 2015 for patients with Viruses that infect bacteria! metastatic melanoma Summary: Viruses vs. Bacteria Characteristic Viruses Bacteria Living No Yes Size Small Large Cell wall No Yes Nucleus No No Ribosomes No Yes Enzymes Maybe Yes Nucleic acid Yes Yes Reproduction Can only Vegetative- binary fission, budding multiply in host Asexual- endospore formation cells Sexual- conjugation, transduction “MODERN” VIRUSES Virus Taxonomy Suffixes ◦ Family: -viridae Family: Herpesviridae ◦ Sub-family: -virinae Genus: Herpesvirus Species: Human herpes virus ◦ Genus: -virus ◦ Species: [Disease] virus CORONAVIRUSES  ◦ Relatively large viral particles VIRAL PARTICLE ◦ Non-segmented, single-stranded RNA ◦ Enveloped with a helical nucleocapsid ◦ Prominent spike proteins Pathogenesis and Replication ◦ Seven serotypes ◦ Four upper respiratory tract = common cold ◦ Three lower respiratory tract = pneumonia → SARS-CoV, SARS-CoV-2, MERS-CoV ◦ SARS-CoV and SARS- CoV-2 attach to human cells with angiotensin-converting enzyme-2 (ACE-2) via spike protein ◦ Protease reveals a fusion protein for entry to cytoplasm ◦ Virion is uncoated and genome translated ◦ New virus assembled in cytoplasm Transmission and Epidemiology* *For general coronaviruses* ◦ Primarily respiratory route via sneezing and coughing ◦ Somewhat from contaminated surfaces ◦ Infection worldwide and early in life ◦ Seasonal outbreaks in winter every 2-3 years Specific Outbreaks SARS-CoV MERS-CoV ◦ Originated in China in November 2002 ◦ Originated in Saudi Arabia in 2012/2013 ◦ “Severe Acute Respiratory Syndrome” ◦ “Middle Eastern Respiratory ◦ Fatality about 9% Syndrome” ◦ Human-to-human transmission ◦ Mortality rate of 35% ◦ Likely originated from animals like the ◦ Bats are thought to be a reservoir with horseshoe bat and civet cat close contact with camels as the mode of transmission to humans Clinical Findings “Common cold” coronaviruses SARS/MERS ◦ Rhinorrhea (runny nose) ◦ Severe atypical pneumonia ◦ Scratchy sore throat ◦ Fever of at least 38°C ◦ Low-grade fever ◦ Nonproductive cough ◦ Lasts for several days ◦ Dyspnea ◦ May also cause bronchitis ◦ Hypoxia ◦ Chills, rigors, malaise, headache ◦ Incubation period 2-10 days (mean 5 days) COVID-19 A Brief Recap of the Pandemic so Far… ◦ December 2019: outbreak of pneumonia in Wuhan, China ◦ Likely originated from a bat coronavirus with pangolin as an intermediate reservoir ◦ NEW strain of coronavirus that the population did not have existing immunity to ◦ WHO declares global pandemic March 11, 2020 ◦ Quickly mutating virus resulting in several variants ◦ As of November 9, 2023: ◦ Approximately 700 million cases ◦ 7 million deaths (1.0%) ◦ 13.5 billion vaccine doses COVID-19: Transmission ◦ Primarily inhalation of respiratory droplets from coughing, sneezing, or talking ◦ May also be in respiratory aerosols (smaller particles than droplets, remain airborne longer) ◦ Viral shedding begins 2-3 days before symptom onset and lasts about 7 days ◦ Can also occur by hand contact with surfaces containing virus ◦ Majority of infection are acquired from asymptomatic carriers (a period about 10 days after infection) ◦ High rates in nursing homes, prisons, and homeless shelters ◦ Less seasonality than influenza virus infections COVID-19: Attachment and Entry ◦ Main receptor is ACE-2, as in other coronavirus infections ◦ Cell surface protease TMPRSS-2 cleaves spike protein to reveal fusion subunit ◦ Antibody (from natural infection or vaccine) prevents this binding of the spike protein ◦ Low number of cases of COVID-19 in children is attributed to low number of ACE-2 receptors ◦ Neuropilin-1 (NRP-1) is a newly identified receptor that spike protein binds to PCR test for viral RNA Nasopharyngeal swab COVID-19: Very sensitive and specific, but could have false negative if too soon after infection Diagnosis Most sensitive 3 days after symptom onset Enzyme immunoassay for viral antigen Looks for spike protein Not as sensitive Rapid, inexpensive, can be done at home Serum test for antibodies to virus IgM (5 days) or IgG antibodies (14 days) Do not indicate virus present Greater than 95% specificity COVID-19: Clinical Findings ◦ Incubation period 2-14 days (mean 5 days) ◦ Main Symptoms: ◦ Fever ◦ Dry cough ◦ Shortness of breath ◦ Possible sore throat ◦ Systemic symptoms: fatigue, shaking, chills, headache, myalgia ◦ “Cytokine Storm” = overproduction of cytokines ◦ About 50% of cases are asymptomatic COVID-19: Risk Factors Co-morbidities: compromised immunity; Older adults, especially Obese patients, Smoking or vaping diabetes; chronic heart, over 70 specifically BMI over 30 history kidney, or respiratory disease Men have more infections than women, In general, children Disproportionately possibly due to have less severe cases Re-infection is possible affects minority testosterone up- and lower mortality populations regulating TMPRSS-2 protease Outpatient COVID-19 Treatments COVID-19: “Long COVID” ◦ Approximately 20% of COVID-19 patients had one or more symptom of Long COVID 3-6 months after diagnosis ◦ Huge variety of symptoms ◦ Cognitive difficulties ◦ Fatigue ◦ Dyspnea ◦ Insomnia ◦ Impaired daily functioning ◦ Women more likely than men COVID-19 Vaccine Schedules ◦ Approved for 6 months and older ◦ mRNA vaccine (Pfizer or Moderna) preferred over Vector Vaccine (J&J) ◦ Bivalent Booster available Sept 2, 2022; “Updated” Vaccine available September 12, 2023 ◦ Age 5 and up ◦ At least 2 months after previous vaccination ◦ “Updated” Vaccines available: ◦ September 12, 2023 for Pfizer and Moderna ◦ October 3, 2023 for Novavax ◦ Now unvaccinated patients only need one dose of vaccine for Pfizer or Moderna, two doses of Novavax MPOX  The Viral Outbreak of 2022 ◦ An orthopoxvirus endemic to Africa, in the same family as smallpox ◦ Most common in Men who have sex with Men (MSM) ◦ Transmission: ◦ Direct contact with monkeypox rash and scabs from a person with monkeypox ◦ Includes contact with their saliva, upper respiratory secretions, and areas around the anus, rectum, or vagina ◦ Not strictly sexually transmitted Two Vaccines are Available ◦ JYNNEOS approved for monkeypox and smallpox ◦ Generally given 0.5mL subcutaneously, though alternative 0.1mL intradermal is used to increase doses ◦ Two doses given one month apart ◦ Likely to cause erythema and induration at ID site, potential for keloid scarring ◦ ACAM2000 approved for smallpox, used for monkeypox under Expanded Access Investigational New Drug protocol ◦ More side effects and contraindications ◦ Fully protected two weeks after finishing sequence ◦ Can be used for prevention or after exposure Clinical Course and Treatment ◦ Typically lasts 2-4 weeks ◦ Symptoms: ◦ Rash/lesions ◦ Fever/Chills ◦ Swollen lymph nodes ◦ Fatigue ◦ Pain related to site of lesions ◦ Isolate! Until all lesions have crusted over and new skin forms ◦ Tecovirimat (TPOXX) ◦ Antiviral approved for Smallpox, emergency use authorization for monkeypox ◦ Only for patients with severe disease or at high risk of severe disease (immunocompromised or with skin conditions) ◦ May prevent severe manifestations and decrease mild symptoms (pain, swelling, scarring)  RESPIRATORY SYNCYTIAL VIRUS Respiratory Syncytial Virus (RSV) ◦ Direct or Indirect via droplets ◦ People are infectious for 3-8 days and may be infectious prior to showing symptoms ◦ Infants, children, and older patients are at increased risk of severe RSV ◦ Children often exposed at school of daycare ◦ Don’t kiss babies! https://www.cdc.gov/rsv/index.html RSV Epidemiology ◦ 2.1 million outpatient visits for children under 5 years old per year ◦ 6,000-10,000 deaths among Older Adults (65 years and older) per year ◦ 100-300 deaths in children under 5 years old per year ◦ Start of season in mid-September to mid-November with peak in late December to mid-February ◦ Season “offset” mid-April to mid-May ◦ Florida has an earlier onset and longer duration than most other regions ◦ Seasonal pattern disrupted by COVID https://www.cdc.gov/rsv/index.html Symptoms and Care Symptoms Treatment ◦ Runny nose ◦ Manage fever and pain ◦ Decrease in appetite (acetaminophen, ibuprofen) ◦ Coughing ◦ Drink fluids ◦ Sneezing ◦ Consult a physician if prescription cold ◦ Fever medications are necessary ◦ Wheezing https://www.cdc.gov/rsv/index.html QUESTIONS? 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