Virology Lecture (3) PDF

VIROLOGY LECTURE (3) By: EMAD TANTAWY  Viral genetic and replication Viruses are lacking an energy-generating system. Small virus has few genes, large viruses have as many as 200 gene. Mutation: error in viral genome, cause subtle genetic changes. DNA viruses are more stable tha...

VIROLOGY LECTURE (3) By: EMAD TANTAWY  Viral genetic and replication Viruses are lacking an energy-generating system. Small virus has few genes, large viruses have as many as 200 gene. Mutation: error in viral genome, cause subtle genetic changes. DNA viruses are more stable than RNA viruses, because of the error correction mechanisms in DNA. Types of mutations: Point, Insertion, and Deletion mutations. Spontaneous mutations: are errors in genome replicating polymerase, or result of incorporation of tautomeric forms of bases (resonance from keto to enol, and from amino to imino). Mutations induced by physical or chemical agents: 1- Physical Agents: such as UV or X-rays. 2- Chemical Agents: acting directly on bases (e.g. nitrous acid), and acting indirectly (e.g. base analogs). Lecture (3) Recombination: occurs when co-infecting viruses exchange genetic information, causing major genetic changes. e.g. exchange between members of the same virus type (2 influenza viruses). 1- Classic recombination: common in DNA viruses, or RNA viruses with DNA phase (e.g. retroviruses). It involves 3 steps: a) Breaking of covalent bonds within the nucleic acid. b) Exchange of genetic information. c) Reforming of covalent bonds. 2- Reassortment: non-classic recombination, occur in segmented- genome viruses (e.g. orthomyxo, reo, arena, and bunya viruses). It is used in some vaccines (e.g. influenza and rotavirus). Lecture (3)  Replication of viruses (1) Attachment and adsorption: surface virus proteins interact with specific receptors on target cell surface. (2) Penetration (Uptake): virus is engulfed inside the cell by: a- Direct translocation across cell membrane. b- Fusion of viral envelope with cell membrane. e.g. paramyxoviruses (measles) and retroviruses (HIV). c- Receptor mediated endocytosis or engulfed in a pinocytotic vesicle (viropexis) in 4 steps: 1. Invagination of host cell membrane. 2. Vesicles formation in cell cytoplasm. 3. Fusion of virus with vesicles membrane by low pH. 4. Releasing of virus (e.g. naked and some enveloped viruses). (3) Uncoating: Release of viral genome from its capsid. Eclipse period: is the period between the end of uncoating stage, and maturation of new viral particles. Lecture (3) (4) Gene expression:  1- Early viral mRNA synthesis (Transcription): a) DNA viruses: use the host cell “DNA-dependent RNA polymerase” to synthesize their mRNA. All DNA viruses are dsDNA, except Parvovirus is ssDNA. b) RNA viruses: each group synthesize mRNA differently: (+)ssRNA: use their genome directly as mRNA (e.g. Poliovirus). (-)ssRNA: carry own “RNA-dependent RNA polymerase” (Influenza). dsRNA: use own polymerase for transcribing into mRNA (Reovirus). (+)ssRNA with DNA intermediate: use their “RNA-dependent DNA polymerase” (RT) to transcribe RNA into dsDNA, which then transcribed into viral mRNA, by host cell RNA polymerase (Retroviruses). Lecture (3)  2- Early viral proteins synthesis (Translation): Viral mRNA is translated by host cell ribosomes into viral protein. Some are early proteins (e.g. enzymes required for replication), some are late proteins (e.g. structural proteins of progeny viruses). (5) Assembly: new virus genomes and proteins are assembled, forming new virus particles. - DNA viruses replicate in nucleus, except Poxvirus replicate in cytoplasm, as it carry its own polymerase. - RNA viruses replicate in cytoplasm, except retroviruses and influenza viruses replicate in nucleus. (6) Release: Enveloped viruses are released by budding from cell, while Unenveloped are released by rupture or lysis of cell. Lecture (3) Thank you