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Viruses II – Interaction with the cells Lecture 90 Mgr. M. Jelínek [email protected] Plan of this lecture 1. Reproduction cycle of viruses 2. Important viral groups Reproduction cycle of viruses • 1. Adsorption of virion on the cell surface and pervase inside • 2. Reproduction of viral macromolecules in a cell • 3. Releasing of matured virions from a cell Enter to a cell across cellular membrane • Fussion of membranes, nucleocapsids is released to cytotoplasm • Receptor mediated endocytosis • Injection of DNA to cytoplasm - bacteriophages Reproduction of viruses in a cell Reproduction (lytic) cycle – virus multiplies in a cell and spreads to other cells, horizontal transmision Virogeny (for bacteriophages lyzogeny) – integration to the genom (integrated NA is called provirus), replication with cellular genom, vertical transmision Mechanism of replication Latence – genom of virus is in the cell, but viral proteins are not expressed, or in very low level 1) Releasing of NA from capsid 2) Syntesis of early proteins 3) Replication of NA 4) Syntesis of late, especialy structural proteins 5) Maturation of virions - autoagregation Perzistence – genom of virus is in cell and a little viral proteins or particles is produced Releasing of virions from cells • During of cell lysis: Iniciated by viral proteins, or by autolytical procceses of damaged cell, necrosis • Exocytosis virions: active procces (budding), virions move to membrane, where are budded and leave cell by exocytosis Results: • Death of cell – necrosis iniciated by viral proteins, iniciated by large budding, apoptosis, • Cytopatic efect: damage of a cell, a tissue, an organ, can be reversible, possibility of cell transformation • Without cell injuring Plan of this lecture 1. Reproduction cycle of viruses 2. Important viral groups Clasification of viruses • There were used system by diseases, hosts, shape... • So-called Baltimor´s scheme is used • Viruses are not divided according to their nucleid acid but replication strategy • Because of a big number of species, viral family are used ds DNA viruses • • • • Papilomaviruses – hogwarts, cervix carcinoma Polyomaviruses: animals Adenoviruses: respiration, gastrointestinalis Herpesviruses: virus herpes simplex 1, virus varicella-zoster, EBV - virus Epstein-Barr) (infection mononukleosis, Burkitt´s lymfoma) • Poxviruses: smallpox/variola A strategy is similar to normal cell´s replication and transcription. Some viruses use cell´s polymerases, some use their own. +ss RNA viruses • Picornaviruses - virus poliomyelititis – polio, hepatitis A, rhinoviruses Vaccination: Salk ´s – inactivated virus 1955 Sabin´ s – atenuated virus 1962 +ss RNA • Flaviviruses – tips born encefalitis, dengue feber, spread by insect, tips or mosquito hepatitis C virus – by body fluids – still no vaccination • Togaviry - rubeolla - ss RNA viruses -ssRNA viruses: • Orthomyxoviruses – influenza A, B segmented genom, others are non - segmented, except of mutations, there is recombinations of fragments Paramyxoviruses - measles, mumps • Rabdoviruses: rabies virus • Filoviruses - ebola, hemohargical febers Reoviruses- dsRNA Typical producing of virospheres – place of intenzive production of viral proteins • Very common children diarrhoea • Strategy similar to RNAviruses Rotavirus Retroviruses a hepadnaviruses • Retroviruses – HIV, HTLV1, Kaposhi sarkom • Hepadnaviruses – hepatitis B Some examples of ANTIVIROTICS • Blocking of decomposition of virus • Influenza virus A Amantadin – blocking of ion channel on surface of capsid • Virus enters a cell, but can not „unpack“ itself • There exists resistance • Inhibition of replication • Mostly analogs of nucleosids – fosforylation • Inhibition of reverse transcription • Viral polymerase is blocked with high specifity than cell´s – possibility of cytotoxicity Mechanism of effect of acyklovir – inhibition of synthesis of viral DNA Acykloguanosin Cyclovir, Herpex, Acivir, Acivirax(), Zovirax, Aciclovir (Sanofi-Aventis) and Zovir (GSK) INHIBITORS of REVERSE TRANSKRIPTASE • Important medicament of HIV a HBV • Azidothymidine (Zidovudine; AZT) • Inhibitors of proteases • HIV proteases – nedeed for maturation of virus • It cleaves viral polyprotein on functional fu proteins, that creates HIV virion • Inhibition of releasing of virus from cells • Influenza A a B, zanamivir – tamiflu