Virology Lecture Notes PDF

Lecture 4/ Virology /7th Semester / Dept. of (MLT) Dr.Sheylan S. Abdullah Viral Genetics: The study of viral genetics falls into two general areas: (1) Mutations and their effect on replication and pathogenesis (2) The interaction of two genetically distinct viruses that infect the sam...

Lecture 4/ Virology /7th Semester / Dept. of (MLT) Dr.Sheylan S. Abdullah Viral Genetics: The study of viral genetics falls into two general areas: (1) Mutations and their effect on replication and pathogenesis (2) The interaction of two genetically distinct viruses that infect the same cell. Mutations Mutations in viral DNA and RNA occur by the same processes of basesubstitution, deletion, and frame shift. Probably the most important practical use of mutations is in the production of vaccines containing live, attenuated virus. These attenuated mutants have lost their pathogenicity but have retained their antigenicity—they therefore induce immunity without causing disease. Most DNA viruses use the DNA synthetic machinery of their host cell and benefit from the proofreading and error-correcting mechanisms that are built into those systems. RNA virus replication is fraught with even more mutation, because viral RNA polymerases possess no proofreading capacity. This provides this group of viruses with impressive genetic plasticity to evolve successful strains in the face of changing environmental pressures. The origination of genetic variants due to mutational change is referred to as antigenic drift (epidemic). There are two other kinds of mutants of interest. The first are antigenic variants such as those that occur frequently with influenza viruses, which have an altered surface protein and are therefore no longer inhibitedby a person's preexisting antibody. The variant can thus cause disease, 1 Page whereas the original strain cannot.  Lecture 4/ Virology /7th Semester / Dept. of (MLT) Dr.Sheylan S. Abdullah The second are drug-resistant mutants, which are insensitive to an antiviral drug because the target of the drug, usually a viral enzyme, has been modified. Some deletion mutants have the unusual property of being defective interfering particles. They are defective because they cannot replicate unless the deletedfunction is supplied by a "helper" virus. They also interfere with the growth of normal virus if they infect first and pre- empt the required cellular functions Defective interfering particles may play a role in recovery from viral infection; they interfere with the production of progeny virus, thereby limiting the spread of the virus to other cells. Viruses Interaction When two or more virus particles infect the same host cell, they may interact in a variety of ways. They must be sufficiently closely related, usually within the same viral family, for most types of interactions to occur. When two genetically distinct viruses infect a cell, three different phenomena can occur. 1. Recombination: Is the exchange of genes between two chromosomes that is based on crossing over within regions of significant base sequence homology (nucleic acid strands break, and part of the genome of one parent is joined to part of the genome of the second parent). Results in the production of progeny virus (recombinant) that carries traits not found together in either parent Recombination can be readily demonstrated for viruses with double- stranded DNA as the genetic material and has been used to determine their genetic map. However, recombination by RNA viruses occurs at a very low frequency, if at all. 2. Reassortment: This occurs only in those viruses which have RNA segmented genomes such as Influenza-virus A and B (8 segments) and Reoviridae (10-12 segments). An exchange of segments occurs between various viruses resulting into synthesis of various stable reassortments. This phenomenon also occurs in nature and results in genetic variation in viruses. This is known as genetic shift, and is responsible for pandemics of disease because the host population does not have immunity to the new, dramatically different variant strain 2 Page  Lecture 4/ Virology /7th Semester / Dept. of (MLT) Dr.Sheylan S. Abdullah 3. Complementation: can occur when either one or both of the two viruses that infect the cell have a mutation that results in a nonfunctional protein. The no mutated virus "complements" the mutated one by making a functional protein that serves for both viruses. Complementation is an important method by which a helper virus permits replication of a defective virus. One clinically important example of complementation is hepatitis B virus providing its surface antigen to hepatitis delta virus, which is defective in its ability to produce its own outer protein. If both mutants are defective in the same gene product, they will not be able to complement each other's growth. Phenotypic mixing: 1. Phenotypic Mixing: When two related viruses infect one cell, it is possible for the capsid proteins of the progeny generation to mix proteins from each of the parental viruses. This is called phenotypic mixing, and because capsid proteins dictate tropism, it may result in altered cellular infection for one generation. 2. Phenotypic Masking (transcapsidation): When two related viruses infect one cell, and the capsid proteins of one parental virus form around the genome of the other, the progeny generation may again express different cellular tropism from 3 Page the parental viruses. This is referred to as phenotypic masking  Lecture 4/ Virology /7th Semester / Dept. of (MLT) Dr.Sheylan S. Abdullah Phenotypic Mixing Phenotypic Masking Pseudotypes, which consist of the nucleocapsid of one virus and the envelope of another e.g nucleocapsid of vesicular stomatitis virus and the envelope of HIV are currently being used in study immune response to HIV. Interference Interference indicates inhibition of growth of one virus in a host when it is simultaneously infected with another virus. This is usually mediated by interferon. In contrast, mixed infections sometimes increase the yield of one virus. This phenomenon is called as enhancement. Several mechanisms have been elucidated as causes of interference: 1. One virus may inhibit the ability of the second to adsorb to the cell, either by blocking its receptors (retroviruses, enteroviruses) or by destroying its receptors (orthomyxoviruses). 2. One virus may compete with the second for components of the replication apparatus (eg, polymerase, translation initiation factor). 3. The first virus may cause the infected cell to produce an inhibitor (interferon) that prevents replication of the second virus 4 Page 14/ Oct/2024