Viruses II – Interaction with the cells Lecture 90 Mgr. M. Jelínek

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 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 Latence – genom of virus is in the cell, but viral proteins are not expressed, or in very low level 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 Very common children diarrhoea Strategy similar to RNA- viruses Typical producing of virospheres – place of intenzive production of viral proteins Rotavirus

Retroviruses a hepadnaviruses Retroviruses – HIV, HTLV1, Kaposhi sarkom Hepadnaviruses – hepatitis B

Blocking of decomposition of virusBlocking 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 Some examples of ANTIVIROTICS

Inhibition of replicationInhibition 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 Cyclovir, Herpex, Acivir, Acivirax(), Zovirax, Aciclovir (Sanofi-Aventis) and Zovir (GSK)Sanofi-AventisGSK Acykloguanosin

INHIBITORS of REVERSE TRANSKRIPTASE Important medicament of HIV a HBV Azidothymidine (Zidovudine; AZT)

Inhibitors of proteasesInhibitors 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 cellsInhibition of releasing of virus from cells Influenza A a B, zanamivir – tamiflu