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Topic 10 Viruses October 21, 2005 Biology 1001 What Are Viruses? • Viruses are infectious particles consisting of nucleic acid enclosed in a protein coat, and sometimes a membranous envelope • As obligate intracellular parasites, viruses are either the most complex macromolecules or the tiniest, simplest forms of life The Discovery of Viruses 1883-1935 • Discovered as the causative agent of tobacco mosaic disease – Sap from diseased leaves causes the disease in new plants – Ruled out a toxin, as the causative agent reproduced in the new plants – Could not isolate or culture a bacterium – Concluded that the particle could only reproduce within a host – The infectious particle was subsequently shown to crystallize and was observed with the electron microscope The Structure of Viruses • The viral genome – The nucleic acid component of the virus is either dsDNA, ssDNA, dsRNA, or ssRNA depending on the virus – A single linear or circular molecule containing a few to several hundred genes – (Details of table for interest only) The Structure of Viruses • The protein coat of viruses is called the capsid – The capsid is rod-shaped, polyhedral or complex in shape – Capsids are built from a large number of one or a few protein subunits called capsomeres • TMV is a helical arrangement of >1000 molecules of a single protein • Adenovirus is a polyhedral capsid of 252 identical protein subunits • The most complex capsids belong to the phages, such as T4 or T2 • The viral envelope, if it exists, is a host-derived phospholipid membrane – Functions to help infect the host – May contain viral proteins and glycoproteins – Encases or cloaks the capsid Figure 18.4 Viral Reproductive Cycles • Viruses can reproduce only within a host cell because they lack the enzymes and ribosomes necessary to make proteins • The range of host cells that a particular virus can infect is called its host range – The host range can be broad (eg. rabies virus can infect humans, bats, dogs, raccoons) or narrow (eg. poliovirus only affects humans) • Host specificity results from the evolution of recognition systems by the virus to receptors on the host cell • In multicellular eukaryotes viruses infect specific tissues or cell types (eg. rhinovirus – human cold virus - infects the upper respiratory tract, poliovirus infects nerve cells, HIV attacks certain white blood cells only) Viral Reproductive Cycles • Overview of a simplified viral reproductive cycle, Fig. 18.5 – A viral infection begins when the genome of a virus enters the host cell – Once inside, the viral genome takes over the cell’s machinery – enzymes, precursors, ribosomes etc. – New viral nucleic acid and new viral proteins are synthesized – New viral particles assemble and exit the host cell, spreading the infection to new host cells Reproductive Cycles of Phage Viruses • Bacteriophages are dsDNA viruses of bacteria • They have two alternate reproductive mechanisms: the lytic cycle and the lysogenic cycle • The lytic cycle culminates in the death of the host and release of hundreds of new phage particles • Phages which can only reproduce lytically are called virulent • During a lysogenic cycle, the phage DNA integrates into the host’s genome where it is called a prophage, and reproduces whenever the bacteria reproduces • A virus such as λ that can enter a lysogenic cycle is called temperate • Ultimately the prophage exits the bacteria genome and initiates a lytic cycle Figure 18.6 The lytic cycle of phage T4, a virulent phage Animation Reproductive Cycles of Animal Viruses • Animal viruses are varied in terms of reproductive cycle – one key feature is type of genome, and another is the presence or absence of a viral envelope (see Table 18.1) • RNA as the genetic material – Retroviruses are a type of ssRNA virus where the RNA acts as a template for DNA synthesis (reverse flow of information) – Retroviruses are packaged with the enzyme reverse transcriptase – The DNA produced by a retrovirus is incorporated as a provirus into the host genome; it is then transcribed into RNA that serves as the mRNA as well as the genome for the next viral generation • Role of the viral envelope – Nearly all animal viruses with RNA genomes also have viral envelopes – During infection, the viral envelope fuses with the host plasma membrane to allow the virus to enter the cell – Viral envelope glycoproteins are made in the host and transported to the cell surface for packaging of new viruses Figures 18.9 & 18.10 - The structure and reproductive cycle of HIV, the retrovirus that causes AIDS New human immunodeficiency viruses exiting a helper T cell Animation Viruses and Disease • Viruses cause disease in animals, plants, bacteria, and fungi – Symptoms caused by damaging or killing cells, producing toxins, or stimulating the host immune system – Range from mild to severe, depending on reproductive cycle, type of tissue or cell, etc. • Major medical intervention is the vaccine, a harmless variant that stimulates the host immune system to mount a preemptive defense – Certain drugs such as acyclovir for herpes resemble nucleosides and interfere with viral nucleic acid synthesis Emerging Viruses • Viruses that appear, or come to the attention of scientists, suddenly SARS – – – – HIV – a retrovirus SARS – a coronavirus Ebola – a filovirus “bird flu”1 – an orthomyxovirus • Three factors contribute to emergence: mutation of existing viruses, spread from one host species to another, spread from a small isolated population Hantavirus – a group V ssRNA virus The Origin of Viruses • Evolution of viruses – Because viruses depend on cells for their own propagation, it is reasonable to assume that they evolved after the first cells – Most molecular biologists favor the hypothesis that viruses originated from fragments of cellular nucleic acids that could move from one cell to another – Candidates for the original sources of viral genomes include plasmids and transposons – Plasmids are small circular DNA molecules, found in bacteria and yeast, that replicate independently from the main chromosome(s) and can be transferred between cells – Transposons are DNA segments that can move from one location to another within a cell’s genome – Viruses, plasmids, and transposons are all mobile genetic elements Are Viruses Alive? • • • • • • • • • • Cell as basic unit of structure? DNA as hereditary material? Growth and development? Reproduction? Regulation/homeostasis? Emergent properties? Evolutionary adaptations? Order? Energy processing? Response to environment?