Neurotropic Viruses Lecture Notes PDF

Dr. Ieva Glāzere Department of Biology and Microbiology Neurotropic viruses. Slow viral infections. Oncogenic viruses. MF 8th lecture 21/04/2020 1 Lecture Outline n Neurotropic viruses: » Rabies » TBE n...

Dr. Ieva Glāzere Department of Biology and Microbiology Neurotropic viruses. Slow viral infections. Oncogenic viruses. MF 8th lecture 21/04/2020 1 Lecture Outline n Neurotropic viruses: » Rabies » TBE n Slow viral infections. » Prions n Oncogenic viruses » DNA oncogenic viruses » RNA oncogenic viruses 2 Rabies / Rhabdovirus 3 Rabies (hydrophobia) § Rabies - an acute fatal infection of CNS § Virus transmission to human from a bite of a rabid animal. Classification: § Family: Rhabdoviridae § Genus: § Lyssavirus Rhabdovirus (rabies lyssavirus) § Vesiculovirus Vesicular stomatitis-like virus 4 Rhabdovirus Morphology § Ø 75 x 180-200 nm; § bullet-shaped particles § ss (-)sense RNA, virions contain RNA-dependent-RNA- polymerase § GP (10 nm) covered super capsid - contains cylindric nucleocapsid 5 Rhabdovirus Antigenic structure 1 serotype, various strains Genome encodes 5 proteins / antigens: § G – glycoprotein receptors, associated in trimers and forms the surface peplomeres. Binds to human receptors, provides receptor-mediated endocytosis. § M - matrix antigen, provides successful budding. § Capsid antigens: § N – nucleoproteins, the main nucleocapsid component, provides bases for polymerase § L – RNA-dependent-RNA-polymerase § P – co-factor for polymerase 6 7 8 9 Negri bodies – rabies viral antigen in the cytoplasm (contains viral nucleoprotein) 10 Rhabdovirus Resistance: n Survives storage at 4oC – weeks. n Killed rapidly by: » Exposure to UV radiation or sunlight » Heat of 50oC – 1 h » Lipid solvents (ether) » Trypsin » Detergents 11 Rhabdovirus Animal susceptibility: wide host range. The virus is widely distributed in infected animals: CNS (!) Saliva Urine Lymph Milk 12 Rhabdovirus Source of infection: 1) Infected wild animals: v Wolves – East-Europe v Foxes – West-Europe v Skunk, raccoons – US, Canada v Bats – Latin America 2) Domestic animals ( developing countries) – virus in saliva 13 14 Rhabdovirus Recovery: very rare, except in certain bats. Transmission: by bite. IP: variable (age, immune status, amount, distance the virus has to travel from its point of entry to the CNS) 15 days – 21 days (7 days – 6 years) 15 Rhabdovirus Virus replication: Attachment to cells via GP spikes Cellular receptor – nicotinic acetylcholine receptor ¯ Receptor endocytosis ¯ Cell cytoplasm – transcription, translation , replication, formation of virus ¯ Budding 16 Rhabdovirus 17 Rhabdovirus Pathogenesis Virus multiplies locally in muscles or connective tissues at the site of inoculation ↓ Enters peripheral nerves at neuromuscular junctions ↓ Spreads up the nerves to the CNS, using retrograde axonal transport (clinical symptoms) ↓ 18 Rhabdovirus Pathogenesis (2) Multiplies in CNS (limbic system, neocortex) ↓ Through peripheral nerves descend to salivary glands (submaxillary !!!) ↓ Other organs (pancreas, kidney, heart etc.) n No viremia! 19  Viral travel rate: 20-40 cm/day 1,2-2,4 cm/day 20 Rhabdovirus Clinical findings: 1. Prodrome: 2-10 days v Malaise v Anorexia v Headache v Photophobia v Sore throat v Vomiting v Abnormal sensation around the site of infection etc. 21 Rhabdovirus Clinical findings (2) 2. Acute neurologic phase: Paralytic form vs furious form n Signs of CNS dysfunction v The act of swallowing precipitates a painful spasm of throat muscles – hydrophobia, aerophobia. v Hallucinations, changed behaviour - nervousness, apprehensions. v Progressive flaccid paralysis. ↓ v Convulsive seizures or coma v Death (2-7 days after onset, due to respiratory paralysis) ↓ n Recovery and survival – extremely rare (