Virus Replication PDF

Replication of Viruses Chapter Six Introduction Viruses multiply only in living host cells (bacteria or animal cells) that provide the energy and synthetic machinery and the low- molecular-weight precursors for the synthesis of viral proteins and nucleic acids. Viruses that infect...

Replication of Viruses Chapter Six Introduction Viruses multiply only in living host cells (bacteria or animal cells) that provide the energy and synthetic machinery and the low- molecular-weight precursors for the synthesis of viral proteins and nucleic acids. Viruses that infect bacteria are called bacteriophages. The viral replication cycle is described in in two different ways: - The first approach is a growth curve, which shows the amount of virus produced at different times after infection. - The second is a stepwise description of the specific events within the cell during virus growth. Viral Growth Curve When a single virion (one virus particle) infects a cell, it can replicate in approximately 10 hours to produce hundreds of virions within that cell This remarkable amplification explains how viruses spread rapidly from cell to cell. The time required for the growth cycle varies (differs); it is minutes for some bacterial viruses and hours for some human viruses. The unique feature of viral multiplication is that soon after entry into a host cell, the infecting virion is disrupted, and its measurable infectivity is lost. This phase of the growth cycle is called the eclipse period  The eclipse period is actually one of intense synthetic activity as the cell is redirected toward fulfilling the needs of the virus. Eclipse period duration varies depending on both the particular virus and the host cell. The eclipse period ends with the appearance of virus Eclipse period is followed by rise period, which is an interval (period) of rapid accumulation of infectious progeny virus particles. Note that infection begins with one virus particle and ends with several hundred virus particles having been produced; this type of reproduction is unique to viruses. After the synthesis of viral nucleic acid and viral proteins, the components assemble to form new infectious virions. The yield of infectious virus per cell ranges widely, from modest numbers to more than 100,000 particles. The duration of the virus replication cycle also varies widely, from 6 to 8 hours (picornaviruses) to more than 40 hours (some herpesviruses).  Not all infections yield intact (complete) infectious progeny Clinical Importance for virus: Latency  Productive infections: occur in permissive cells (able to Upon initial infection, some viruses establish latent infection. Latent infection allows support the expression of all viral genes) and result in the viral infections to be maintained for the life of the host. production of infectious virus. During latency, the genome of the virus is present in cells, but infectious progeny  Abortive infections: FAIL to produce infectious progeny, are not recovered. either because the cell may be nonpermissive or because the infecting virus may be defective. Latent infection is different from chronic infection in that the viral genome is not replicating and virions are not produced.  Latent infection: in which viral genome replication and expression are at minimum or delayed, leading to During latency there is minimal viral gene intracellular viral persistence in the host cell and the host expression. Latent genes encode functions for maintenance of the virus inside the cell remains intact. The latent period is the time from the host cell, preventing host cell death and inhibiting the host immune response. onset of infection to the appearance of virus Moreover, the viruses; latent genes direct the extracellularly. expression process to NOT produce antigens that could be recognized by the host immune system.  Alterations of cell morphology accompanied by marked disorder of cell function begin upon the END of the latent period. This cytopathic effect (CPE) ends in the lysis and death of cells. CPE can be seen under the microscope and, when observed, is an important initial step in the laboratory diagnosis of viral infection. Not all viruses cause CPE; some can replicate while causing little morphologic or functional change in the cell. Diagnostic application for CPE Virus growth in cell culture frequently produces a CPE that can provide a presumptive diagnosis. CPE is a change in the appearance of the virus- infected cells. This change can be in such features as (1) size, (2) shape, and (3) the fusion of cells to form multinucleated giant cells (syncytia). CPE is usually a manifestation of virus-infected cells that are dying or dead. The TIME taken for the CPE to appear and the TYPE of cell in which the virus produces the CPE are important clues in the presumptive identification. Specific events within the cell during virus growth. Viral replication in eukaryotic cells The infecting parental virus particle attaches to the cell membrane and then penetrates (enter) the host cell. The viral genome is “uncoated” by removing the capsid proteins, and the genome is free to function. Early mRNA and proteins are synthesized; the early proteins are enzymes used to replicate the viral genome. Late mRNA and proteins are then synthesized. These late proteins are the structural, capsid proteins. The progeny virions are assembled (put together) from the replicated genetic material, and newly made capsid proteins and are then released from the cell. 1. Early events Attachment Penetration Uncoating 2. Middle events Gene expression Genome replication 3. Late events Assembly Release  Attachment, Penetration & Uncoating The virus particle penetrates (enters) by being engulfed in a pinocytotic vesicle (cell drinking) or ENDOCYTOSIS, within which the process of uncoating begins. A low pH within the vesicle Favors uncoating. Rupture of the vesicle or fusion of the outer layer of virus with the vesicle membrane deposits viral nucleic acid into the cytoplasm, and called infectious nucleic acid. Infectious nucleic acid is purified viral DNA or RNA that can carry out the entire viral growth cycle and result in the production of complete virus particles. Which includes pinocytosis  The proteins on the surface of the virion attach to specific receptor proteins on the cell surface through weak, noncovalent bonding The specificity of attachment determines the host and organ tropism of the virus. Some viruses have a narrow range, whereas others have quite a broad range. Tropism of a virus pertains to the types of cells, tissues, and animal and plant species in which it can replicate For example, poliovirus can enter the cells of ONLY humans, whereas rabies virus can enter ALL mammalian cells. Those cellular receptors that have been identified are surface proteins that serve other functions. For example, herpes simplex virus type 1 attaches to the fibroblast growth factor receptor, rabies virus to the acetylcholine receptor, and human immunodeficiency virus (HIV) to the CD4 protein on helper T lymphocytes.  Most of DNA viruses replicate in the nucleus and use the host cell RNA polymerase to synthesize their mRNA. The genome of all DNA viruses consists of double-stranded DNA, except for the parvoviruses, which have a single-stranded DNA genome. Most RNA viruses undergo their entire replicative cycle in the cytoplasm, except HIV and infleunzae virus. The genome Gene Expression of all RNA viruses consists of single-stranded RNA, except for members of the reovirus family, which have a double-stranded RNA & Genome genome. Replication Once the viral mRNA 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 the viral genome) and others of which are late proteins (i.e., structural proteins) of the progeny viruses. As the replication of the viral genome proceeds (continues), the structural capsid proteins to be used in the progeny virus particles are synthesized. Assembly and Release Maturation, during which the assembly of newly synthesized viral components into complete virions. Release, the departure of new virions from host cells. Release generally, but NOT always, kills (lyses) host cells. General Steps in Viral Replication Cycles in bacterial cells (Bacteriophages) Lytic cycle: viral particles are made and released when the host cell lyses. Lysogenic cycle: viral genome replicates as the host cell genome is replicated