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 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 –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 & The structure and reproductive cycle of HIV, the retrovirus that causes AIDS Animation New human immunodeficiency viruses exiting a helper T cell

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 pre- emptive 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 –HIV – a retrovirus –SARS – a coronavirus –Ebola – a filovirus –“bird flu” 1 – an orthomyxovirus 1 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 SARS

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?