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13-b Viruses pp. 387-415 *Animation: Viral Replication The Microbiology Place Viral Replication (Viral Replication Quiz) Interactive Tutorials Lytic Cycle Lysogenic Cycle DNA Viruses RNA Viruses Viruses 2 The viral genome ‘directs’ the host’s metabolic machinery in order to multiply Virus contains only: Nucleic acid DNA or RNA genes for just a few things 1. Structural components, e.g., capsid proteins 2. Few enzymes, e.g., lysozyme, reverse transcriptase, integrase, protease Virus needs the following from the host cell: tRNA Ribosomes, amino acids, nucleotides All enzymes for: 1. Viral protein & enzyme synthesis, catabolism 2. ATP energy production 3 The basic mechanism of viral multiplication is similar for all viruses Bacterial virus Lytic cycle Lysogenic cycle Bacteriophage (BF) T-even BF Lambda () Animal virus DNA RNA Herpesviridae Retroviridae 4 Bacteriophage Multiplication BF viruses exhibit 2 types of life cycles • A lytic cycle – Lyses & kills host cell E. coli – Virus name: T-even bacteriophages (T2, T4, T6) • A lysogenic cycle – Does not lyse or kill the host cell – Incorporates DNA into host cell’s DNA • Called a prophage – Remains ‘inactive,’ or latent – Virus name: lambda () 5 T-even BF – Lytic Cycle Stages Name Process 1 2 Attachment Penetration Phage attaches to host cell using tail fibers Phage lysozyme opens cell wall, tail sheath contracts forcing tail core and DNA into cell 3 Biosynthesis Phage DNA directs production of viral components by host cell Maturation Assembly of phage particles Release Phage lysozyme breaks cell wall (to ‘escape’) 4 5 See Fig. 13.11 6 1. Attachment 2. Penetration 3. Biosynthesis 4. Maturation 5. Release 7 BF Lambda () – Lysogenic Cycle May proceed through a lytic stage But, also incorporate DNA into the host cell’s DNA to begin a lysogenic cycle – The inserted DNA now called a prophage • During lysogeny, prophage remains latent • Bacterial host cell is called a lysogenic cell – Host cell is immune to re-infection by the same phage – But, not immune to infection by other phages 8 Fig. 13.12 Lysogenic cycle of bacteriophage in E. coli • Incorporates DNA into host cell’s DNA, begins lysogenic cycle. • Phage remains inactive. • Host cells called lysogenic cells. 9 Result of Lysogeny – Phage Conversion Host cells exhibit new properties Bacteria are able to produce toxins when they carry a lysogenic phage (prophage) Bacteria Disease Corynebacterium diphtheriae Streptococci Clostridium botulinum Diphtheria Scarlet fever Botulism Vibrio cholera Cholera 10 Overview: RNA Virus Multiplication Name Process 1 2 Attachment Entry Virus attach to cell membrane By endocytosis or fusion 3 Uncoating By viral or host enzymes, separates NA from protein coat 4 5 6 Biosynthesis Maturation Release Production of NA and proteins NA and capsid proteins assemble By budding (enveloped viruses) or rupture 11 Attachment, Entry, Uncoating Pinocytosis Fusion 12 Figure 13.14a, b Release of Virus, ‘Budding’ Figure 13.20a, b 13 RNA Virus Multiplication - Retroviridae RNA-containing viruses gp120 HIV 14 HIV Attachment, Entry HIV glycoprotein Binds to CD4+ receptor HIV glycoprotein, gp120 Viral RNA CD4+ Receptor Cell membrane Virus fuses to cell membrane Viral RNA is released into cell 15 HIV ‘Budding’ • Viral proteins • Implant in the cell membrane • Virus buds off • Carries some membrane • Studded with proteins • That recognize, infect new cells Drawing: Russell Kightley Media 16 Capsid Envelope Reverse Transcriptase 2 identical + RNA strands 8. Budding 1. Attachment 2. Entry 3. Uncoating Host DNA RT 7. Viral proteins processed Viral RNA Viral DNA 4. DNA synthesis Provirus Viral proteins 5. RNAv, into nucleus, integrates 6. Transcription HIV Multiplication Figure 13.19 17 HIV Infection Viral RNA transcribed into viral DNA (RT) Viral DNA integrated into DNAc of host cell 1. Generates active infection 2. May not produce new HIV, remains ‘hidden’ as a provirus 3. HIV produced by host cell may also remain as latent viruses in vacuoles within the host cell Can persist for decades Ch. 19, p. 568 4. Provirus or latent virus within host cell is sheltered from the immune system (AB’s) 5. Reverse transcriptase enzyme step has a high mutation rate – – – Lack ‘proofreading’ capability Mutations probably introduced at every position in the HIV genome Indicates the challenges to vaccine / drug development Ch. 19, p. 568 19 Active HIV Infection Ch. 19, p. 568-9 20 Latent HIV Infection Latent Activated Ch 19, p. 568-70; Figure 19.14 a, b 21 Progression of HIV Infection From initial HIV infection to AIDS takes about 10 years (in US) – Devastates the immune system Many diseases associated with HIV infection – Protozoa (Cryptosporidium, Toxoplasma) – Viruses (CMV, Herpes simplex) – Bacteria (Mycobacterium [TB]) – Fungi (Pneumocystis, Histoplasma, Candida) – Cancers (Kaposi’s sarcoma) 22 Latent & Persistent Viral Infections • Latent – Virus remains in asymptomatic host cell for long periods – Herpesviruses: cold sores, shingles • Persistent – Disease processes occurs over a long period; generally is fatal – Morbillivirus (measles virus): Subacute sclerosing panencephalitis 23 24 25 Q: 1. This figure shows an enveloped virus. During which phase of the life cycle is this envelope acquired? a) Penetration b) Biosynthesis c) Attachment d) Release 2. Which of the following is not used for classification of viruses? a) Size b) Disease symptoms a) Nucleic acid b) Method of replication 26 Q: 1. The following steps occur during bacteriophage replication. What is the second step? a) Lysis b) Penetration c) Biosynthesis d) Attachment 2. What is the name given to viral DNA incorporated into a lysogenic cell? a) Bacteriophage b) Latent phage c) Oncogenic virus d) Prophage 27 Q: 1. What is the name of the process that involves both the release and the enveloping of the virus? a) Lysogeny b) Budding c) Conjugation d) Reverse transcription 2. During lysogeny, the phage remains latent. a) True b) False 3. Viruses range in size from 20 to 1000 nm in length, and are easily seen using a compound light microscope. a) True b) False 28 Q: 1. HIV can evade the immune system by all of the following means except which one? a) Remaining in vacuoles b) Forming a provirus c) Destroying the host’s antibodies d) Infecting by cell-cell fusion 2. HIV infects the CD8 T cells as well as CD4 cells. a) True b) False 3. Heterosexual sex is the most common form of HIV transmission. a) True b) False 29 Definitions Budding: process which forms the envelop around the capsid release of the enveloped virus through the plasma membrane of an animal cell Lytic cycle: A mechanism of phage multiplication that results in host cell lysis Lysogenic cycle: Stages in viral development that result in the incorporation of viral DNA into host DNA Lysozyme: A BF enzyme capable of hydrolyzing bacterial cell walls Persistent viral infection: a disease process that occurs gradually over a long time Phage: another name for bacteriophage, a virus that infects bacterial cells Phage conversion: genetic change in the host cell resulting from infection by a BF Pinocytosis: the engulfing of virus by infolding of the plasma membrane Prophage: phage DNA inserted into the host cell’s DNA, ‘pops’ out of DNA to initiate the lytic cycle Provirus: viral DNA integrated into the host cell’s DNA, but never comes out of the chromosome and is protected from the host’s immune system and 30 antiviral drugs Viral Infections – Swine Flu HA: Hemagglutinin NA: Neuraminidase PA: RNA polymerase subunit PB1: RNA polymerase subunit PB2: RNA polymerase subunit NP: Nucleoprotein M: Matrix protein, M1, M2 NS: Non-structural proteins CDC Influenza Laboratory, May 2009 31 • Hemagglutinin – – – – Responsible for binding the virus to the cell Also cause RBC’s to clump together At least 16 different HA antigens (H1-H16) The first 3, H1, H2, H3 are found in human influenza viruses • Neuraminidase – Catalyze hydrolysis of terminal sialic acid residues from viruses and host cell receptors – Nine influenza subtypes known (N1-N9) – N1, N2, N3 known in humans • Matrix proteins – Structural proteins linking viral envelope to virus core 32 • New strain contains genes from 4 different flu viruses • The CDC identified 4 component strains as: – North American swine influenza – Swine influenza typically found in Asia, Europe – North American avian influenza – Human influenza • Human populations have not been vaccinated or naturally immunized 33 • Pigs are susceptible to influenza viruses that also infect birds and humans • Act as a ‘mixing vessel’ allowing reassortment • Re-assortment: (swap genes) – Viral genome has 8 independent pieces of RNA – The 8 strands of RNA from different viruses can mix together – The reassorted strain will share properties of its predecessors – And form a new type of virus 34 • New strain appears to be result of reassortment of these viruses: – Human influenza – Swine influenza • Genetic characterization: – HA gene similar to swine flu viruses in the US – NA & M genes similar to swine versions in EU • The HA in the new virus comes from pigs – But some of the other genes come from bird and human • The CDC calls the mixture ‘very unusual’ 35