VIRUSES Chapter 19

What is a virus? A virus is a submicroscopic infectious particle composed of a protein coat (capsid) and a nucleic acid core (either DNA or RNA). Viruses are similar in size to a large protein macromolecule, generally smaller than 200 nm in diameter.

Discovery of Viruses Search for cause of tobacco mosaic disease led to viruses Beijerinck proved that the disease was caused by a virus. The elusive virus was crystallized in 1935 by Wendell Stanley.

Beijerinck’s experiment Fig. 19-2 Beijerinck’s experiment RESULTS 1 Extracted sap from tobacco plant with tobacco mosaic disease 2 Passed sap through a porcelain filter known to trap bacteria 3 Rubbed filtered sap on healthy tobacco plants Figure 19.2 What causes tobacco mosaic disease? 4 Healthy plants became infected

Viral Capsids Capsids are built from protein subunits called capsomeres May be rod-shaped (helical viruses), polyhedral (icosahedral viruses) or more complex Some viruses have membranous envelopes that help them infect hosts (flu virus) Bacteriophages, also called phages, infect bacteria

RNA DNA Membranous envelope Head RNA Capsomere DNA Capsid Tail sheath Fig. 19-3 RNA DNA Membranous envelope Head RNA Capsomere DNA Capsid Tail sheath Capsomere of capsid Tail fiber Glycoprotein Glycoproteins 18  250 nm 70–90 nm (diameter) 80–200 nm (diameter) 80  225 nm Figure 19.3 Viral structure 20 nm 50 nm 50 nm 50 nm (a) Tobacco mosaic virus (b) Adenoviruses (c) Influenza viruses (d) Bacteriophage T4

Viruses are obligate intracellular parasites, which means they can reproduce only within a host cell Each virus has a host range, a limited number of host cells that it can infect

Viral Reproduction Once a viral genome has entered a cell, the cell begins to manufacture viral proteins using the host cell’s materials (enzymes, ribosomes, tRNAs, amino acids, ATP, etc.) ** RNA viruses may have codes for their own enzymes however.

VIRUS Entry and uncoating DNA Capsid Transcription and manufacture Fig. 19-4 VIRUS Entry and uncoating 1 DNA Capsid Transcription and manufacture of capsid proteins 3 2 Replication HOST CELL Viral DNA mRNA Viral DNA Capsid proteins Figure 19.4 A simplified viral reproductive cycle Self-assembly of new virus particles and their exit from the cell 4

Phages are the best understood of all viruses Phages have two reproductive mechanisms: the lytic cycle and the lysogenic cycle http://www.nsf.gov/news/news_videos.jsp?org=NSF&cntn_id=100420&media_id=51295

The Lytic Cycle The lytic cycle culminates in the death of the host cell by producing new phages and digests the host’s cell wall, releasing the progeny viruses A phage that reproduces only by the lytic cycle is called a virulent phage Bacteria have defenses against phages, including restriction enzymes that recognize and cut up certain phage DNA

Attachment Entry of phage DNA and degradation of host DNA Release Fig. 19-5-5 1 Attachment 2 Entry of phage DNA and degradation of host DNA 5 Release Phage assembly Figure 19.5 The lytic cycle of phage T4, a virulent phage 4 Assembly 3 Synthesis of viral genomes and proteins Head Tail Tail fibers

The Lysogenic Cycle The lysogenic cycle replicates the phage genome without destroying the host The viral DNA molecule is incorporated into the host cell’s chromosome and is called a prophage. Every time the host divides, it copies the phage DNA and passes the copies to daughter cells Viruses that can be lysogenic or lytic are called temperate phages.

The phage injects its DNA. Fig. 19-6 Daughter cell with prophage Phage DNA The phage injects its DNA. Cell divisions produce population of bacteria infected with the prophage. Phage DNA circularizes. Phage Bacterial chromosome Occasionally, a prophage exits the bacterial chromosome, initiating a lytic cycle. Lytic cycle Lysogenic cycle The bacterium reproduces, copying the prophage and transmitting it to daughter cells. The cell lyses, releasing phages. Lytic cycle is induced or Lysogenic cycle is entered Figure 19.6 The lytic and lysogenic cycles of phage λ, a temperate phage Prophage New phage DNA and proteins are synthesized and assembled into phages. Phage DNA integrates into the bacterial chromosome, becoming a prophage.

Animal Viruses Classified as DNA or RNA viruses, single or double-stranded Many have envelopes with glycoproteins that are specific for receptors. The glycoproteins are made by the ER and added to the host cell’s membrane which envelopes the emerging viruses.

Notice the viral mRNA codes for Glycoproteins that are added to Fig. 19-7 Capsid and viral genome enter the cell Capsid RNA HOST CELL Envelope (with glycoproteins) Viral genome (RNA) Template mRNA Notice the viral mRNA codes for Glycoproteins that are added to the cell membrane. RNA viruses often have Codes for their own enzymes unlike DNA Viruses. Capsid proteins ER Copy of genome (RNA) Glyco- proteins Figure 19.7 The reproductive cycle of an enveloped RNA virus New virus

Table 19-1a Table 1

Table 19-1b Table 1

RNA Viruses The broadest variety of RNA genomes is found in viruses that infect animals Retroviruses use reverse transcriptase to copy their RNA genome into DNA (HIV is ex.) The viral DNA that is integrated into the host genome is called a provirus Unlike a prophage, a provirus remains a permanent resident of the host cell http://highered.mcgraw-hill.com/olcweb/cgi/pluginpop.cgi?it=swf::535::535::/sites/dl/free/0072437316/120088/micro41.swf::HIV Replication

Fig. 19-8a Glycoprotein Viral envelope Capsid RNA (two identical strands) RNA DNA Reverse transcriptase HOST CELL HIV Reverse transcriptase Viral RNA RNA-DNA hybrid DNA NUCLEUS Provirus http://highered.mcgraw-hill.com/olcweb/cgi/pluginpop.cgi?it=swf::535::535::/sites/dl/free/0072437316/120088/micro41.swf::HIV Replication Chromosomal DNA RNA genome for the next viral generation Figure 19.8 The reproductive cycle of HIV, the retrovirus that causes AIDS mRNA New virus

Membrane of white blood cell HIV HIV entering a cell Fig. 19-8b Membrane of white blood cell HIV Figure 19.8 The reproductive cycle of HIV, the retrovirus that causes AIDS 0.25 µm HIV entering a cell New HIV leaving a cell

Evolution of Viruses Since viruses can reproduce only within cells, they probably evolved as bits of cellular nucleic acid Candidates for the source of viral genomes are plasmids and transposons (small mobile DNA segments) Mimivirus, a double-stranded DNA virus, is the largest virus yet discovered…. not any more…. Mega Virus

Mimivirus and megavirus Mimivirus was first isolated in 1992 from amoeba growing in a water tower. Megavirus was isolated from infecting amoeba with mimiviruses. Which came first, the cell or the mimivirus?

How fast can viruses evolve? When viruses face an obstacle to infecting the cells they normally infect, how long does it take for them to evolve to successfully invade them again? A new study has a frightening answer: just a little more than two weeks. how fast viruses evolve – lambda virus

Viral diseases in animals Symptoms caused by - toxins - body’s defense mechanisms Vaccines – weakened or derivatives of viral particles capable of causing an immune response Antibiotics not effective Some antiviral medications interfere with viral nucleic acid synthesis

Why are antibiotics ineffective against viruses? They target 70s ribosomes, cell walls, or bacteria-specific enzymes High rates of mutation in viral protein coats and enzymes make it difficult to develop vaccines and drugs against viruses

Where do new viruses come from? Mutations of existing viruses The dissemination of an existing virus to a more widespread population Or spread between species Epidemic – general outbreak of a disease Pandemic – global epidemic

(a) The 1918 flu pandemic (b) Influenza A H5N1 virus Fig. 19-9 (a) The 1918 flu pandemic 0.5 µm Figure 19.9 Influenza in humans and other animals For the Discovery Video Emerging Diseases, go to Animation and Video Files. (b) Influenza A H5N1 virus (c) Vaccinating ducks

Plant viruses More than 2,000 types of viral diseases of plants are known and cause spots on leaves and fruits, stunted growth, and damaged flowers or roots Most plant viruses have an RNA genome Plant viral disease can spread by vertical transmission from parent plant or by horizontal transmission from an external source.

Fig. 19-10 Figure 19.10 Viral infection of plants

Viroids and Prions: The Simplest Infectious Agents Viroids are circular RNA molecules that infect plants and disrupt their growth Prions are slow-acting, virtually indestructible infectious misfolded proteins that cause brain diseases in mammals Prions propagate by converting normal proteins into the prion version Scrapie in sheep, mad cow disease, and Creutzfeldt-Jakob disease in humans are all caused by prions

Viroids in Plants

Misfolding of proteins to form prions Fig. 19-11 Misfolding of proteins to form prions Remember: Prion - Protein Original prion Prion Aggregates of prions New prion Normal protein Figure 19.11 Model for how prions propagate

Scrapie in sheep

How Prions Arise

Why is it hard to treat viroid and prion infections? Due to their simple structure, it is difficult to attack them without attaching native cell proteins or RNA

Hybrid Viruses hybrid viruses avian-human flu viral replication