Viral Replication Cycle PDF

Viral Replication Cycle Virus Genetics Interactions Among viruses Lecture 3  Viral Replication Stages of viral Growth cycle 1- Attachment and penetration 2- Uncoating of the viral genome 3- Early viral mRNA synthesis 4- Early viral protein synthesis 5-...

Viral Replication Cycle Virus Genetics Interactions Among viruses Lecture 3  Viral Replication Stages of viral Growth cycle 1- Attachment and penetration 2- Uncoating of the viral genome 3- Early viral mRNA synthesis 4- Early viral protein synthesis 5- Viral genome replication 6- Late viral mRNA synthesis 7- Late viral protein synthesis 8- Progeny virion assembly 9- Virion release from the cell  Attachment and penetration specific viruses use specific cellular receptors on the cell surface and therefore are very specific in the cell type that they can infect – ‘cell tropism’ and is important in disease pathogenesis (i.e. why some viruses affect certain organs only). Examples: HSV-1 attaches to the fibroblast growth factor receptor, Influenza viruses use the haemagglutinin (HA) protein to attach to the sialic acid-containing oligosaccharides on the cell surface  Attachment and penetration Viruses may use more than one cell receptor, for example HIV uses the CD4 receptor to attach to the CD4 Th cells, and to a chemokine receptor CCR5 as a co-receptor. Most viruses use more than one receptor on the cell surface in a sequential binding process. The virus particle penetrates by being engulfed in a pinocytotic vesicle, for enveloped viruses, by fusion of their lipid envelope with the cell membrane.  Uncoating of the viral genome Before the virus replication, the viral genome has to be exposed by removal of the associated viral proteins. This is usually mediated by the endocytosed viral particle merging with cellular lysosomes The resulting drop in pH dissociates the viral genome from its binding protein Then rupture of the vesicle deposits the inner core of the virus into the cytoplasm.  Early viral mRNA synthesis A-In DNA viruses: (with one exception) they replicate in the nucleus and use the host cell DNA-dependant-RNA polymerase to synthesize their mRNA (only poxviruses replicate in the cytoplasm).  Early viral mRNA synthesis B-In RNA viruses: RNA viruses undergo their entire replicative cycle in the cytoplasm. Except retroviruses and influenza viruses have important replicative step in the nucleus. RNA viruses fall into four groups with quite different strategies for synthesizing mRNA:  1.Single stranded RNA viruses of positive sense: these viruses use their RNA genome directly as mRNA. 2.Single stranded RNA viruses of negative sense: these viruses transcribe their mRNA using the negative strand as a template; the virus carries its own RNA- dependent-RNA polymerase. 3. Double stranded RNA viruses: have to first convert the –ve RNA strand of the DS RNA into a complementary RNA to be used as mRNA. The +RNA strand of the DS RNA acts as a template for viral genome replication. These viruses also need to carry the RNA-dependent RNA polymerase to initiate the first steps of viral replication,so the virus carries its own RNA-dependent-RNA polymerase, eg Reovirus 4. Retroviruses: have single stranded RNA of positive sense that is transcribed into double stranded DNA by RNA dependant DNA polymerase (reverse transcriptase RT) carried by the virus. (hence the name, retro = reverse) (The normal transcription is always from DNA to RNA) This DNA is then transcribed into viral mRNA by host cell RNA polymerase, in which this DNA is integrated into the host cell DNA.  Early viral protein synthesis Once viral mRNA of either DNA or RNA viruses is synthesized, it is translated by host cell ribosomes into viral proteins, some of which are early proteins i.e. enzymes required for replication of viral genome, and others are late proteins i.e. structural proteins of the progeny viruses (the terms early and late mean occurring before and after replication of the genome respectively).  Viral genome replication Most viruses make virus-encoded polymerase that make many copies of the parental genome that become the genome of the progeny virions.  Late viral mRNA synthesis Late viral protein synthesis Progeny virion assembly by packaging the viral nucleic acid within the capsid proteins (late proteins).  Virion release from the cell By either of two processes: Rupture of the cell membrane and release of mature virus particles (usually in un-enveloped viruses) Release of the viruses by budding through the outer cell membrane in enveloped viruses (except in herpes family in which budding from the nuclear membrane)  Virus Genetics Interactions Among viruses 1. Recombination & Reassortment. 2. Genetic reactivation (Marker rescue). 3. Complementation. 4. Phenotypic mixing. 5. Interference. Recombination: crossing over between the two chromosomes of different viruses infecting the same cell resulting in progeny virus carries trait not found in either parents. Reassortment: in viruses with segmented genomes, resulting in much higher frequency of gene exchange than does recombination, Reassortment of influenza virus RNA segments is involved in the major antigenic changes which are the bases of recurrent influenza epidemics. Genetic reactivation (Marker rescue): between the genome of active virion and inactivated virus genome, so that certain markers of the inactivated parent are rescued and appear in the progeny. Complementation: one virus provides a gene product in which the second is defective, allowing the second virus to grow. The genotypes of the two viruses remain unchanged. Phenotypic mixing: The genome of one virus randomly incorporated in the capsid proteins of a different virus or a capsid conssits of components of both viruses. Interference: Infection of cells or animal with two viruses leading to inhibition of multiplication of one of the viruses. Several mechanisms of Interference: A-One virus inhibit the ability of the second to adsorb to the cell either by blocking its receptors or destroying its receptors. B-One virus may compete with the other for components of replication apparatus e.g. polymerase enzyme. C-The first virus cause the infected cell to produce an inhibitor (interferon).