VPViro_L7_AB_Summer2023 (1).pdf

Intro to Micro: Virology Lecture 7 – RNA 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 in...

Intro to Micro: Virology Lecture 7 – RNA 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. RNA viruses Virus taxonomy Overview of DNA & RNA viruses What to know/family?! Ø Ø Ø Ø Virus DNA or RNA? Specific characteristic Important members Diseases RNA viruses Retroviridae § Characteristics § Linear (+)sense ss RNA § Icosahedral capsid § Envelope with gag-proteins § Release by budding § Transmission § Cell-to-cell § Fluids § Airborne (e.g. Jaagsiekte) § Pseudodiploid genome = 2 identical linear (+)sense ss RNA strands § Retro = reverse/backward § RNA is reverse-transcribed to DNA-intermediates via reverse transcriptase (RT) § Retrovirus DNA is inserted in host genome as provirus Retroviridae Retroviridae RNA -> DNA -> RNA -> polypeptide Retroviridae Retroviridae § Three important viral enzymes § Reverse transcriptase (RT) § Integrase: integration of viral DNA into host’s genome § RNA polymerase II (RNAPII): proteolytic cleavage during virion maturation § Active cells are required for building in the genetic material § EXCEPT genus Lentivirus: can integrate in non-dividing host cells § Retroviridae infect a wide range of animals including humans § Associated with immunodeficiency syndromes and cancer § Oncovirus = any virus with DNA or RNA genome causing cancer § Proto-oncogene = gene that encodes for proteins regulating cell growth and differentiation and that can become an oncogene (gene potentially causing cancer) Retroviridae Retroviridae: mechanism of transformation § Proto-oncogenes mistakenly incorporated into provirus § Disruption of cellular proto-oncogenes (e.g. viral promoter triggers overexpression) Infection of cell & integration of proto-oncogene Acutely transforming retrovirus Infection of new host cell Viral oncogene Proto-oncogene Slowly transforming retrovirus Integration and expression of viral oncogene Infection with retrovirus carrying promoter gene Neoplastic transformation Integration of promoter gene adjacent to proto-oncogene Conversion of proto-oncogene to oncogene Retroviridae Retroviridae § Different groups within the Retroviridae FYI No malignant transformation Chronic immunodeficiencies No disease association in vivo Retroviridae Avian leukosis § Genus Alpharetrovirus, species Avian sarcoma leucosis virus (ASLV or ALV) § Host: poultry § Lymphoid leukosis and lymphoma (blood cell tumor from lymphocytes) Retroviridae Enzootic nasal tumor § Genus Betaretrovirus, species Enzootic nasal tumor virus (ENTV) § Host: sheep, goats § Tumors in the nasal epithelium Retroviridae Jaagsiekte § Genus Betaretrovirus, species Jaagsiekte sheep retrovirus (JSRV) § Host: sheep, goats § Contagious lung cancer or ovine pulmonary adenocarcinoma: respiratory distress when you chase animal Retroviridae Bovine leukosis § Genus Deltaretrovirus, species Bovine Leukemia Virus (BLV) § Host: cattle § Enlargement of lymph nodes (e.g. retro-ocular -> protrusion of conjunctival membrane) Retroviridae Equine Infectious Anemia, Swamp Fever § Genus Lentivirus, species Equine infectious anemia virus (EIAV) § Host: equidae § Anemia, thrombocytopenia, fever, weight loss, swelling of legs § Mechanical vectors: stable flies! USA Reportable disease Retroviridae Feline Leukemia § Genus Gammaretrovirus, species Feline Leukemia Virus (FeLV) § Host: felids § Transmission: close contact with nasal or saliva secretions, to a lesser extent through milk & blood § Infection in utero possible § Asymptomatic carriers (0.5% of pet cats) à risk to others! Retroviridae Feline Leukemia § Clinical signs: lethargy, fever, stomatitis, opportunistic infections, bone marrow disorders § Immunosuppression or in final stage lymphomas § More progressive than FIV § Vaccines and more intense testing à decline of prevalence of FeLV infections Retroviridae Feline immunodeficiency § Genus Lentivirus, species Feline Immunodeficiency Virus (FIV) § Host: cats (2.2-4.4% infected worldwide), endemic in African lions § Transmission: bite injuries (saliva) § Virus infects CD4-T cells, CD8-T cells, B cells and macrophages à depletion of CD4-T cells Retroviridae Feline immunodeficiency § Clinical signs: attack on immune system à anemia, low white blood cell count à secondary infections, cancer, neurological diseases Retroviridae Feline immunodeficiency § Diagnosis: detection of antibodies à seropositive § Control: spaying or neutering cats (no need for euthanasia – consensus USA) Chhetri et al., 2013. BMC Vet Res, 9 (2). Proportional Morbidity Ratio of FIV to FeLV § Blue border: FIV infection > FeLV infection § Red border: FeLV infection > FIV infection Retroviridae RNA viruses Rhabdoviridae § Characteristics § Linear (-)sense ss RNA § Helical nucleocapsid § Enveloped § Bullet-shaped § Release by budding § Ribonucleoprotein complex: RNA bound by viral nucleoprotein § Negri body: eosinophilic, inclusion bodies found in the cytoplasm of infected nerve cells § Hosts: (in)vertebrates § Cell tropism: neurons à neurovirulent virus § Transmission: animal bite à saliva (rabies) § Present in all continents except Antarctica and Australia Rhabdoviridae Rabies § Genus Lyssavirus, species Rabies Virus § Reservoir: dogs, cats, wild canids & felids, bats, mongooses § Animal bite à initial replication in myocytes à transport through peripheral nerves à central nervous sytem à neuronal infection! § Virus is shed in saliva of infected animals § Slow-moving virus (~ distance bite to brain) § Incubation time: 3-8w in dogs Rhabdoviridae Rabies § After virus reaches brain, three phases are defined: § Prodomal Phase (2-3 days): nervousness, anxiety, solitude, different behavior (friendly -> irritable; aggressive -> affectionate). Licking of bite side is mostly observed. § Furious Phase (1-7 days): restless, irritable, hyperresponsive to visual and auditory stimuli, roaming, disoriented. § Paralytic Phase: salivate (inability to swallow), deep labored breathing, paralyzed facial muscles, respiratory failure and death Rhabdoviridae Rabies § Direct fluorescent antibody test: look for presence of Rabies virus antigens in brain tissue § Not in the blood!!! Rhabdoviridae Rabies ZOONOSIS Rhabdoviridae RNA viruses Orthomyxoviridae § Characteristics § Segmented linear (-)sense ss RNA § Enveloped with spikes § Release by budding § Glycoprotein spikes § Neuraminidase = NA = N § Haemaglutinin = HA = H § Three genera defined by antigenic differences in nucleoprotein and matrixprotein § Influenza virus A: humans, birds, mammals (pandemics!) § Influenza virus B: humans, seals § Influenza virus C: humans, pigs, dogs Orthomyxoviridae Orthomyxoviridae § International nomenclature of influenza viruses Host of origin (if human no host of origin) Orthomyxoviridae Flu epi- & pandemics § Influenza A subtypes are defined by H & N spikes § Multiple strains within a subtype Orthomyxoviridae Flu epi- & pandemics § Reassortment = mixing of genetic material of species into new combinations, resulting in a reassortant virus Orthomyxoviridae Flu epi- & pandemics FYI Orthomyxoviridae Flu epi- & pandemics HOW the flu virus can change: “shift” and “drift” § Antigenic drift = small changes in the genes that happen continually over time as the virus replicates (Influenza A, Influenza B) § Closely related viruses share antigenic properties à cross-protection § Accumulation of changes over time à immune system does no longer recognize virus (renew influenza vaccines!) § Antigenic shift = abrupt, major genetic changes in Influenza A viruses, resulting in new HA and/or new NA proteins à new Influenza A subtype Orthomyxoviridae Flu epi- & pandemics Orthomyxoviridae Swine flu § Influenza A virus (common) & Influenza C virus (rare) § Influenza B virus has not been reported § Transmitted via direct contact (virus survives up to 3 months in pigs) Prevent spread to humans: vaccinatio n of pigs & sanitary control RNA viruses Filoviridae § Characteristics § Linear (-)sense ss RNA § Pleomorphic or filamentous § Helical nucleocapsid § Enveloped with spikes § Reservoir: fruit bats; occasional humans, primates § Geography: Central Africa and South Asia § Transmission: contact with body fluids § Cytopathic infection (i.e. structural changes) in cultured cells and in target organs of host Filoviridae Ebola § Genus Ebolavirus § Haemorrhagic fever, fatality rate 50-90% § Infection of monocytes à release of cytokines à endothelial injury à haemorrhage § Ebola outbreak 2014-2016 (Individual humanity!) ZOONOSIS Filoviridae Ebola FYI Filoviridae Ebola Filoviridae Marburg haemorrhagic fever § Genus Marburgvirus § Haemorrhagic fever in humans and non-human primates § Bleeding all over the body § Who is at risk? § Hospital staff, vets, travelers § Close contact fruit bats and non-human primates § Transmission from animal to human: bat faeces and aerosols § Transmission from human to human: direct contact body fluids ZOONOSIS Filoviridae Marburg haemorrhagic fever RARE HUMAN DISEASE! PREVENTION: § Barrier nursing techniques = prevent direct contact § Awareness Learning objectives RNA VIRUSES 1. Know the different RNA virus families and their basic characteristics § Retroviridae § Rhabdoviridae § Orthomyxoviridae § Filoviridae 2. Understand specific features that lead to differences in replication strategy for retroviridae 3. Understand the specific viral features that lead to flu pandemics (reassortment; antigenic shift and drift) 4. Outline the main characteristic of each viral disease 5. Explain the pathogenesis in FeLV, FIV and Rabies