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Intro to Micro: Virology Lecture 4 & 5 – DNA viruses Anne A.M.J. Becker, DVM, MSc, PhD Associate Professor of Microbiology [email protected] Disclaimer The material used in this presentation has been obtained from different sources including books, published papers and online resources. It i...

Intro to Micro: Virology Lecture 4 & 5 – DNA viruses Anne A.M.J. Becker, DVM, MSc, PhD Associate Professor of Microbiology [email protected] Disclaimer The material used in this presentation has been obtained from different sources including books, published papers and online resources. It is intended only for educational purposes. Most of the presented material comes from the following books: § Veterinary Microbiology and Microbial Diseases, Quiin et al., 2nd ed. § Veterinary Microbiology, Scott et al., 3rd ed. § Infectious diseases of the Dog and Cat, Greene, 4th ed. Figure and material acknowledgement to Dr. David Bemis and Dr John Prescott. Virus taxonomy Virus taxonomy What’s in a name? Virus taxonomy What’s in a name? Naming by disease symptoms and lesions? Bluetongue (sheep) Classical Swine Fever (pigs) Foot and Mouth disease (cattle) African Swine Fever (pigs, warthogs) Virus taxonomy What’s in a name? CONFUSION What if… SAME DISEASE, DIFFERENT NAMES § Classical Swine Fever -> most of the world § Hog Cholera -> USA § Pig Plague -> German ‘Schweinepest’ Virus taxonomy What’s in a name? CONFUSION What if… DIFFERENT DISEASE, SAME NAMES Foot and Mouth Disease Picornaviridae – Enterovirus, Coxsackievirus Picornaviridae - Aphtovirus Virus taxonomy What’s in a name? § Taxonomy: science of naming, describing and classifying organisms § Baltimore’s classification (based on the viral genome) § International Committee on Taxonomy of Viruses (ICTV) § Genome § Replication strategies § Morphology Passport Order (-virales) Family (-viridae) Subfamily (-virinae) Genus (-virus) Species Virus taxonomy Overview of DNA & RNA viruses What to know/family?! Ø Ø Ø Ø Virus DNA or RNA? Specific characteristic Important members Diseases DNA viruses DNA viruses Adenoviridae § Characteristics: § Linear ds DNA § Non-enveloped, icosahedral § Fibers at vertices § Release by lysis § Transmission: droplets, fecal-oral § Epidemiology § Canine adenovirus 1 (CAV1) § Infectious canine hepatitis § Canine adenovirus 2 (CAV2) § Infectious tracheobronchitis (‘Kennel cough’) § Several adenoviruses § Respiratory infections in cattle, sheep, goats, pigs, horses § Vaccines available (CAV2-attenuated live virus strains cross-protect against CAV1) Adenoviridae Infectious Canine Hepatitis (CAV1) § Canine adenovirus 1 § Potentially fatal in unvaccinated puppies § Affects liver, kidneys, eyes and vascular endothelium § Hepatitis § Vasculitis § Keratoconjunctivitis Multifocal haemorrhage in canine lungs Acute liver necrosis Adenoviridae Infectious Canine Hepatitis (CAV1) For initial puppy vaccination (< 16 weeks), one dose of vaccine containing modified live virus (MLV) CPV, CDV, and CAV-2 is recommended every 3-4 weeks from 6-8 weeks of age, with the final booster being given no sooner than 16 weeks of age. For dogs older than 16 weeks of age, two doses of vaccine containing modified live virus (MLV) CPV, CDV, and CAV-2 given 3-4 weeks apart are recommended. After a booster at 6 months to one year, revaccination is recommended every 3 years thereafter. Adenoviridae Infectious tracheobronchitis (Kennel Cough) § Canine adenovirus 2 § Bacteria as primary or secondary infection § Bordetella bronchiseptica, Pseudomonas spp., E. coli § Dry, harsh, hacking cough due to tracheobronchitis § Increased mucus production, nasal or eye discharge § Fever, loss of appetite DNA viruses Poxviridae § Characteristics § Linear ds DNA § Cytoplasmic replication § Intra-cellular mature virus, extracellular enveloped virion § Release by lysis or budding § Transmission: direct contact, fomites, droplets (smallpox), insects § Largest and complex animal virus § Presence of intracytoplasmic inclusion bodies are hallmark of infection POX = any of several viral diseases producing a rash of pimples that become pus-filled and leave pockmarks on healing. Many poxviruses manifest as skin lesions. Poxviridae Fowl Pox, Pigeon Pox § Avipoxvirus Poxviridae Swine Pox § Suipoxvirus § Transmitted by biting louse (Haematopinus suis) à eradication of lice is important Poxviridae Rabbit Myxomatosis § Leporipoxvirus § Spreads through mosquitoes, fleas, biting flies and direct contact with infected animals Poxviridae Rabbit Myxomatosis A genius or bad plan? § Use of virus to control rabbits in Australia (released in 1950) (~ Europe 1952) § Initial mortality rates > 90% and epidemic continued for 4 years with high mortality rates § Now: selection for resistant rabbits and endemic disease! Poxviridae Squirrel Fibroma § Parapoxvirus § Pox in red squirrels with fatal outcome Poxviridae Goatpox, Sheeppox, Bovine Lumpy Skin Disease § Capripoxvirus Poxviridae ORF, Scabby Disease, Thistle Disease, Sore Mouth § Parapoxvirus species Orf virus § Primarily contagious pustular dermatitis in sheep and goat Poxviridae ORF, Scabby Disease, Thistle Disease, Sore Mouth § Parapoxvirus species Orf virus § Primarily contagious pustular dermatitis in sheep and goat ZOONOTIC ! Poxviridae Cowpox § Orthopoxvirus species Cowpox virus § Mostly in cattle (and cats!) Poxviridae Cowpox § Orthopoxvirus species Cowpox virus § Mostly in cattle (and cats!) ZOONOTIC ! Poxviridae Cowpox HISTORY! Vaccination (Jenner, 1762): lat. Vaccinus = meaning of/ from the cow Variolae vaccinae = smallpox of the cow (cowpox) Poxviridae Smallpox, Red Plague § Orthopoxvirus species Variola virus variant major (mortality > 30%) and minor Having considered the development and results of the global program on smallpox eradication initiated by WHO in 1958 and intensified since 1967 … Declares solemnly that the world and its peoples have won freedom from smallpox, which was a most devastating disease sweeping in epidemic form through many countries since earliest time, leaving death, blindness and disfigurement in its wake and which only a decade ago was rampant in Africa, Asia and South America. — World Health Organization, Resolution WHA33.3 (statement 1980) Poxviridae Smallpox, Red Plague § Vaccinia virus in weakened form in smallpox vaccine > cross-protective immune response! § Only two labs are allowed to have smallpox virus for research § Centers for Disease Control and Prevention (CDC) in USA § Russian State Centre for Research on Virology and Biotechnology in Russia § Concern for bioterrorism § Last natural outbreak in 1977 § People born after 1972 have not been routinely vaccinated § No single country has all capacity to respond to public health emergencies caused by epidemics and ‘new’ diseases § Multi-doses of vaccine in readiness Poxviridae Monkeypox § Genus Orthopoxvirus species Monkeypox virus § Natural host reservoir: monkeys(?), rodents § Transmission to humans (zoonotic!) § Direct contact with blood, bodily fluids, cutaneous or mucosal lesions of infected animals § Bites, scratches § Consumption of raw or improperly cooked (bush)meat Poxviridae WHO declares Monkeypox Global Emergency July 23rd, 2022 Poxviridae Monkeypox FYI No historically reported monkeypox Historically reported monkeypox Global Status of Human Cases of Monkeypox Virus (as of 26 July 2022, Source: CDC, USA) Poxviridae Monkeypox FYI No historically reported monkeypox q Bahamas: 1 q Dominican Republic: 3 q St. Lucia: 1 (flight crew member entering country) q Martinique: 1 q Jamaica: 1 q Barbados: 1 Poxviridae Monkeypox § Human-to-human transmission § Direct contact with lesions, body fluids and respiratory droplets § Vertical transmission § Skin-to-skin, face-to-skin, mouth-to-skin § Ignored African problem (outbreaks 2017; cases 2018-2021) § à 2022: 15,593 cases in 68 countries with no history § Preventative measures! § Isolate at home when infected. § Vaccination with smallpox vaccine (85% protection) DNA viruses Parvoviridae § Characteristics § Linear ss DNA § Parvo = “small” § Non-enveloped, stable § Release by lysis § Can only replicate autonomously in actively cycling cells (e.g. erythrocyte progenitors, intestinal crypt cells, lymphoid cells). Otherwise, co-infection with Adenovirus or Herpesvirus. § Transmission: respiratory, oral droplets of fecal-oral route § Epidemiology § Human parvovirus B19: erythema infectiosum (fifth disease) in children, polyarthropathy in adults Parvoviridae Canine parvovirus § Protoparvovirus species Canine parvovirus 2 § Generalized disease in puppies (80% fatal) Enteritis, myocarditis (rarely), lymphopenia Splenomegaly Parvoviridae Other parvoviruses § Feline panleukopenia virus (FPV): generalized disease (feline infectious enteritis) in kittens with panleukopenia and cerebellar hypoplasia § Mink enteritis virus (MEV): leukopenia and enteritis in mink § Aleutian disease virus (ADV): highly contagious fatal disease in mink and ferrets, with splenomegaly, lethargy, bleeding, spontaneous abortion and death § Goose parvovirus (GP) & Muscovy Duck parvovirus (MDP): Goose Plague, Goose Hepatitis, Goose, Derzy’s disease. Highly contagious, causing myocarditis, hepatitis, myositis § Porcine parvovirus (PPV): reproductive failure with no maternal signs Parvoviridae Parcine parvovirues & Feline panleukopenia virus § Parvovirus infections of the fetus (pig or cat) or newborn (dog or cat) result in widespread infection and tissue destruction à developmental defects Porcine parvovirus infection: stillbirth, mummification, embryonic death & infertility (SMEDI syndrome) Feline panleukopenia virus: cerebellar hypoplasia DNA viruses Herpesviridae § Characteristics § Linear ds DNA § Tegument § Enveloped § Envelope by budding at nucleus membrane § Release by exocytosis § Hosts: insects, reptiles, amphibians, mollusks, almost all bird and mammal species (8 types in humans) § Infections typically produce severe diseases in neonates, fetuses and immunocompromised individuals Herpesviridae Herpesviridae § Typically cause latent infections, with intermittent or continuous virus shedding § Virus in neuronal cell bodies § Viral DNA released into neuronal nucleus and circularizes à circular viral DNA persists in the neuronal cell nucleus Herpesviridae Herpesviridae Species Disease Transmission Suid herpesvirus (SuHV-1) Aujeszky’s disease Pseudorabies (USA) Nose-to-nose contact, aerosols Bovine herpesvirus (BoHV-1) Infectious bovine rhinotracheitis (IBR) Nose-to-nose contact, aerosols Gallid herpesvirus (GaHV-1, GaHV-2) Avian laryngotracheitis (GaHV-1) Marek’s disease (GaHV-2) Aerosolized dust Canine herpesvirus (CHV-1) Hemorrhagic disease in puppies Airborne (sneezing) Human herpesvirus (HHV-3) = Varicella zoster virus Chickenpox (varicella) Direct contact, airborne transmission Herpes simplex virus (HHV-1, HHV-2) Cold sore (HHV-1) (Genital) herpes (HHV-2) Direct contact with lesions & fluids, sexual Human herpesvirus (HHV-4) = Epstein-barr virus Infectious mononucleosis (kissing disease) Saliva, sexual, transplacentary Herpesviridae IBR & Aujezky’s Disease § Different symptoms depending on Herpesvirus type and host species IBR: typical ‘red nose’ Aujeszky’s disease Herpesviridae Marek’s Disease § Different syndromes in chickens Ocular lymphomatosis: lymphocyte infiltration of the iris, unequal pupils, blindness Cutaneous Marek’s disease: swollen feather follicles Herpesviridae Herpesviridae § Species-jumping: Herpes, not so quite species-specific after all?! Jerka & Lars EHV1 EHV9 EHV1 How?! Not stable in environment 68m away from each other, different personnel Other hosts as carriers?! (e.g. mice, rodents,…) Zebra-derived herpesvirus § recombinant = genetic material of two different viruses DNA viruses Papillomaviridae § Characteristics § Circular ds DNA § Non-enveloped, small § Release by desquamation § Transmission: sexual or close direct contact § Several hundred species (‘types) in mammals, birds, snakes,... § Highly host- and tissue-specific (cell tropism: epithelial cells of skin or mucous membranes) § Infections are either asymptomatic or causing benign tumors = warts or papilloma’s § Some lesions may transform and become malignant! Papillomaviridae Papillomaviridae Normal vs papilloma infected epithelium: maintain cell division during cell differnetiation Papillomaviridae Papilloma’s DNA viruses Polyomaviridae § Characteristics § Circular ds DNA § Non-enveloped § Release by lysis § Transmission: aerosolized dust, contaminated feces, egg transmission § Hosts: mammals and birds § Cell-tropism: respiratory system, kidneys, brain § Epidemiology § Budgerigar fledgling disease polyomavirus (BFD) § Simian polyomavirus S40 (SV40) Polyomaviridae Polyomaviridae Budgie affected by Polyomavirus SV40: A cancer-causing monkey virus hidden in polio vaccines?! DNA viruses Hepadnaviridae § Characteristics § Partially ds circular DNA § Enveloped § Reverse transcriptase § Release by exocytosis § Transmission: parenteral, sexual, blood § Hosts: humans, apes, birds § Cell-tropism: hepatocytes § Epidemiology § Hepatitis B virus Hepadnaviridae Hepatitis B § Acute Hepatitis B infection § Chronic Hepatitis B infection Don’t mix up with Hepatitis A virus, enterovirus beloning to Picornaviridae! DNA VIRUSES § Adenoviridae § Pox viridae § Parvoviridae § Herpesviridae 3. Understand the specific viral features that lead to the different clinical signs § Papillomaviridae 4. Outline the main characteristic of each viral disease § Polyomaviridae § Hepadnaviridae Learning objectives 1. Know the 7 different DNA virus families and their basic characteristics 2. Understand specific features that lead to differences in replication strategy for each family 5. Explain latent infections in Herpesviridae 6. Exemplify the use of viruses, cross-reactivity and vaccination in eradication of diseases

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