Chapter 6 An Introduction to Viruses Introduction All life-forms can be infected by viruses. Some viruses generate serious epidemics, from dengue fever to influenza to AIDS. Others fill essential niches in the environment, particularly in marine ecosystems. In research, viruses have provided both tools and model systems in molecular biology. This 11-inch-high limestone Egyptian funerary stele is from Saqqara, 10 miles south of Cairo; Amarna Period, 18th Dynasty (1403-1365 BCE), Glyptotek Museum, Copenhagen. The stele portrays Roma (or Rema), an Egyptian doorkeeper, and his family giving offerings to the Goddess Astarte. Thought to be the earliest depiction of a victim of poliomyelitis, the man adeptly carries a goblet while supporting himself with a staff. His withered right leg and deformed right foot are characteristic of poliomyelitis. Ramses V, Pharaoh of Egypt He died ~1145 BCE, presumably of smallpox. His mummified head and torso bear the characteristic lesions of the disease. Smallpox victims included many other rulers throughout history, among them Louis XV of France, Mary II of England, and the Holy Roman Emperor Joseph I. The search for the elusive virus Louis Pasteur postulated that rabies was caused by a virus (1884) Ivanovski and Beijerinck showed a disease in tobacco was caused by a virus (1890s) Viruses: non-cellular particles with a definite size, shape, and chemical composition Viral diseases led to the development of some of the first vaccines. Poliovirus causes poliomyelitis, which can lead to paralysis. President Franklin Roosevelt established the March of Dimes. With its support, Jonas Salk developed the first polio vaccine in 1952. What Is a Virus? A virus is a non-cellular particle that must infect a host cell (obligate intracellular parasite), where it reproduces. It typically subverts the cell’s machinery and directs it to produce viral particles. The virus particle, or virion, consists of a single nucleic acid (DNA or RNA) contained within a protective protein capsid. The position of viruses in the biological spectrum There is no universal agreement on how and when viruses originated Viruses are considered the most abundant microbes on earth Viruses played a role in the evolution of Bacteria, Archaea, and Eukarya Viruses are obligate intracellular parasites Viruses infect all forms of life Viruses are ubiquitous in all environments and part of our daily lives Most frequent infections of college students: 1) Respiratory pathogens such as rhinovirus (the common cold) and Epstein-Barr virus (infectious mononucleosis) 2) Sexually transmitted viruses such as herpes simplex virus (HSV) and papillomavirus (genital warts) Different viruses infect every group of organisms Each species of virus infects a particular group of host species, or host range Viroids Viroids are RNA molecules that infect plants. They have no protein capsid. Are replicated by host RNA polymerase. Some have catalytic ability. Prions Prions are proteins that infect animals. They have no nucleic acid component. Have an abnormal structure that alters the conformation of other normal proteins Extremely resistant to usual sterilization techniques Prions Diseases Common in animals Scrapie in sheep and goats Bovine spongiform encephalopathies (BSE), a.k.a. mad cow disease - transmissible and fatal neurodegenerative disease Humans – Creutzfeldt-Jakob Syndrome (CJS) Viral structure Viruses bear no resemblance to cells Lack protein-synthesizing machinery Viruses contain only the parts needed to invade and control a host cell Virus structure The viral capsid is the protein shell of a virus. The capsid encloses the viral genome The capsid delivers the viral genome into the host cell. Different viruses make different capsid forms. Capsids All viruses have capsids (protein coats that enclose and protect their nucleic acid) The capsid together with the nucleic acid is the nucleocapsid Each capsid is made of identical protein subunits called capsomers Some viruses have an external covering called an envelope; those lacking an envelope are naked Structural types of capsids Helical – Rod or thread-like continuous helix of capsomers forming a cylindrical nucleocapsid Structural types of capsids Icosahedral - Polyhedral with 20 identical triangular faces Have a structure that exhibits rotational symmetry Envelope In some icosahedral viruses, the capsid is enclosed in an envelope, formed from the cell membrane. The envelope contains glycoprotein spikes, which are encoded by the virus. Spikes are essential for attachment of the virus to the host cell Between the envelope and capsid, tegument proteins may be found. Viruses lacking an envelope are naked Dr.Stepehen Fuller Functions of capsid 1. Protect genome from atmosphere (May include damaging UV-light, shearing forces, nucleases either leaked or secreted by cells). 2. Virus-attachment protein- interacts with cellular receptor to initiate infection. 3. Delivery of genome in infectious form. May simply “dump” genome into cytoplasm (most +ssRNA viruses) or serve as the core for replication (retroviruses and rotaviruses). Viruses with unusual structures These have complex multipart structures T4 bacteriophages: Have an icosahedral “head” and helical “neck” Poxviruses lack a typical capsid and are covered by a dense layer of lipoproteins Viruses with unusual structures Filamentous viruses The capsid consists of a long tube of protein, with the genome coiled inside Vary in length, depending on genome size Include bacteriophages (e.g. M13) as well as animal viruses (Ebola) Ebola virus Bacteriophage M13 Bacteriophage Bacterial viruses (phages) Most widely studied are those that infect Escherichia coli – complex structure, DNA Are called T-even phages as T2, T4 & T6 of the 7 phages studied have similar structures Types of viruses Nucleic acids Viral genome – either DNA or RNA but never both Carries genes necessary to invade host cell and redirect cell’s activity to make new viruses Number of genes varies for each type of virus – few to hundreds Nucleic acids • DNA viruses Usually double stranded (ds) but may be single stranded (ss) Circular or linear • RNA viruses Usually single stranded, may be double stranded, may be segmented into separate RNA pieces RNA genomes ready for immediate translation are positive-sense RNA RNA genomes that must be converted into proper form are negative- sense RNA Viral enzymes Pre-formed enzymes may be present – Polymerases – DNA or RNA – Replicases – copy RNA – Reverse transcriptase – synthesis of DNA from RNA (HIV-1) Viral replication- rules All viruses require a host cell for reproduction. Thus, they all face the same needs for host infection: Host recognition and attachment Genome entry Assembly of progeny virions Exit and transmission Replication cycle of Bacteriophages Multiplication goes through similar stages as animal viruses Only the nucleic acid enters the cytoplasm - uncoating is not necessary (Hershey- Chase experiment) Release is a result of cell lysis induced by viral enzymes and accumulation of viruses - lytic cycle Hershey- Chase experiment http://scarc.library.oregonstate.edu/coll/pauling/dna/index.html Steps in phage replication 1. Adsorption – binding of virus to specific molecules on host cell 2. Penetration – genome enters host cell 3. Replication – viral components are produced 4. Assembly – viral components are assembled 5. Maturation – completion of viral formation 6. Lysis & Release – viruses leave the cell to infect other cells Bacteriophages attach to host cells Contact and attachment are mediated by cell-surface receptors. Proteins that are specific to the host species and which bind to a specific viral component. Bacterial cell receptors are normally used for important functions for the host cell. Example: sugar uptake Phage reproduction within host cells Bacteriophages (phages) inject only their genome into a cell through the cell envelope. The phage capsid remains outside, attached to the cell surface (ghost). Orlova EV. How viruses infect bacteria? The EMBO Journal 2009;28(7):797-798. doi:10.1038/emboj.2009.71. Bacteriophages can undergo two different types of life cycles 1) Lytic cycle Bacteriophage quickly replicates, killing host cell 2) Lysogenic cycle Bacteriophage is quiescent. Integrates into cell chromosome, as a prophage. Can reactivate to become lytic. The “decision” between the two cycles is dictated by environmental cues In general, events that threaten host cell survival trigger a lytic burst Lysogeny: The silent virus infection • Not all phages complete the lytic cycle • Some DNA phages, called temperate phages, undergo adsorption and penetration but don’t replicate • The viral genome inserts into bacterial genome and becomes an inactive prophage – the cell is not lysed • Prophage is retained and copied during normal cell division resulting in the transfer of temperate phage genome to all host cell progeny – lysogeny • Induction can occur resulting in activation of lysogenic prophage followed by viral replication and cell lysis Lysogeny • Lysogeny results in the spread of the virus without killing the host cell • Phage genes in the bacterial chromosome can cause the production of toxins or enzymes that cause pathology – lysogenic conversion – Corynebacterium diphtheriae – Vibrio cholerae – Clostridium botulinum Animal Virus replication cycles The primary factor determining the life cycle of an animal virus is the form of its genome. DNA viruses Can utilize the host replication machinery RNA viruses Use an RNA-dependent RNA-polymerase