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I. Viral Genomes © 2015 Pearson Education, Inc. 9.1 Size and Structure of Viral Genomes • Viral genome size (Figure 9.1) • Smallest circovirus: 1.75-kilobase single strand • Largest megavirus: 1.25-megabase pairs • Viral genomes (Figure 9.2) • Either DNA or RNA genomes • Some are circular, but most are linear © 2015 Pearson Education, Inc. © 2015 Pearson Education, Inc. Figure 9.1 9.1 Size and Structure of Viral Genomes • Classification Based mainly on idea proposed by David Baltimore (Baltimore Scheme) • Depends on relationship of genome to mRNA • Genome structure is the key feature © 2015 Pearson Education, Inc. Transcription Genome replication Class I & VII dsDNA (±) virus Class II ssDNA (+) virus Class III dsRNA (±) virus Class IV ssRNA (+) virus Class V ssRNA (–) virus Class VI ssRNA (+) retrovirus Transcription of the minus strand Synthesis of the minus strand Transcription of the minus strand Used directly as mRNA Transcription of the minus strand Reverse transcription dsDNA intermediate dsDNA intermediate (replicative form) mRNA (+) DNA Viruses RNA Viruses Class I classical semiconservative Class II classical semiconservative, discard (–) strand Class VII transcription followed by reverse transcription Class Class Class Class © 2015 Pearson Education, Inc. Transcription of the minus strand III make ssRNA (+) and transcribe from this to give ssRNA (–) complementary strand IV make ssRNA (–) and transcribe from this to give ssRNA (+) genome V make ssRNA (+) and transcribe from this to give ssRNA (–) genome VI make ssRNA (+) genome by transcription of (–) strand of dsDNA Figure 9.2 II. Viruses with DNA Genomes • 9.6 Uniquely Replicating DNA Animal Viruses • 9.7 DNA Tumor Viruses © 2015 Pearson Education, Inc. 9.6 Uniquely Replicating DNA Animal Viruses • Double-stranded DNA animal viruses that have unusual replication strategies • Pox viruses • Adenoviruses © 2015 Pearson Education, Inc. 9.6 Uniquely Replicating DNA Animal Viruses • Pox viruses • Among the most complex and largest animal viruses known (Figure 9.11) • Variola virus (Smallpox virus) most famous • Vaccinia virus in lab, other pox viruses in nature • DNA replicates in the cytoplasm © 2015 Pearson Education, Inc. Pox viruses are ds DNA Viruses that replicate in The cytoplasm What do they need to do this? © 2015 Pearson Education, Inc. 9.6 Uniquely Replicating DNA Animal Viruses • Adenoviruses • Major group of icosahedral, linear, double-stranded DNA viruses • Cause mild respiratory infections in humans • DNA replicates in the nucleus • Replication requires protein primers and avoids synthesis of a lagging strand (Figure 9.12) • Two unusual characteristics © 2015 Pearson Education, Inc. Terminal protein 5′ 3′ Adenovirus DNA C + – C 3′ 5′ C 3′ 5′ Plus strand is copied. 5′ 3′ C – + – C 5′ 3′ 3′ C + – – C C Direction of cyclization – 3′ 5′ 3′ © 2015 Pearson Education, Inc. 5′ C Minus strand is copied. – 5′ 5′ 3′ C 5′ 5′ Minus strand cyclizes via inverted terminal repeats. – 5′ 3′ New synthesis leading strand 5′ C C C + New synthesis leading strand + – Completed linear double strand C 3′ 5′ Figure 9.12 • Covalently linked protein TP • pTP is primer • Strand displacement replication • Viral proteins © 2015 Pearson Education, Inc. 9.7 DNA Tumor Viruses • Some DNA viruses can induce cancer (“tumor viruses or “oncoviruses” • Human Papilloma Viruses (HPV) • Herpesviruses © 2015 Pearson Education, Inc. 9.7 DNA Tumor Viruses • HPV • Nonenveloped icosahedral virionNo enzymes in the virion; replicates in host nucleus • Basal skin cells • 8 kbp DNA is circular (Figure 9.13a) • Small genome, has overlapping genes © 2015 Pearson Education, Inc. 9.7 DNA Tumor Viruses • Some papilloma viruses cause cancer • In most infected host cells, virus infection results in the formation of new virions and the release from host cell • In a few infected host cells, the virus DNA becomes integrated into host DNA (analogous to a prophage), genetically altering cells in the process (Figure 9.13b) • Integrated virus DNA can inactivate cellular tumor suppressor genes or express its own tumor activator genes © 2015 Pearson Education, Inc. Infection Tumor virus DNA + Host DNA Viral DNA Viral DNA integrates into host DNA. Transcription of tumor-inducing genes Tumor virus mRNA Transport of mRNA to cytoplasm and translation Viral tumor-induction proteins © 2015 Pearson Education, Inc. Transformation of cell to tumor state Figure 9.13b 9.7 DNA Tumor Viruses • Herpesviruses • Large group of viruses that cause diseases in humans and animals • Initial infection may be symptomatic or asymptomatic • Virus remains hidden or “latent” for extended periods of time © 2015 Pearson Education, Inc. 9.7 DNA Tumor Viruses • Some Herpesviruses cause cancer • Epstein-Barr Virus • HHV-8 • Diverse mechanisms © 2015 Pearson Education, Inc. III. Viruses with RNA Genomes • 9.11 Viruses That Use Reverse Transcriptase © 2015 Pearson Education, Inc. 9.11 Viruses That Use Reverse Transcriptase • Retroviruses (RNA viruses) and hepadnaviruses (DNA viruses) use reverse transcriptase for replication • Key first step in virus replication cycle • Reverse Transcriptase • Enzyme activity that converts ss RNA into ds DNA © 2015 Pearson Education, Inc. 9.11 Viruses That Use Reverse Transcriptase • Retroviruses (cont'd) • Genome RNA reverse transcribed to dsDNA • Inserts into chromosome • Provirus • Gene expression and protein processing are complex (Figure 9.22) • Gag, pol, env gene regions common to all retroviruses • Retroviruses that cause cancer often have an extra gene region “src” © 2015 Pearson Education, Inc. RNA tumor virus genome • Src is an “oncogene” • C-src = normal cellular version • V-src = version carried by virus © 2015 Pearson Education, Inc. © 2015 Pearson Education, Inc. © 2015 Pearson Education, Inc. © 2015 Pearson Education, Inc. 9.11 Viruses That Use Reverse Transcriptase • Hepadnaviruses • Virions small, irregular-shaped particles (Figure 9.23a) • Include hepatitis B • Can lead to liver cancer • Viral replication occurs through an RNA intermediate • Unusual genomes • Tiny • Only partially double-stranded (Figure 9.23b) © 2015 Pearson Education, Inc. IV. Subviral Agents • 9.12 Viroids • 9.13 Prions © 2015 Pearson Education, Inc. 9.12 Viroids • Viroids: infectious RNA molecules that lack a protein coat • Smallest known pathogens (246–399 bp) • Cause a number of important plant diseases (Figure 9.24) • Small, circular, ssRNA molecules (Figure 9.25) • Do not encode proteins; completely dependent on host-encoded enzymes © 2015 Pearson Education, Inc. 9.13 Prions • Prions: infectious proteins whose extracellular form contains no nucleic acid • Known to cause disease in animals (transmissible spongiform encephalopathies) • Host cell contains gene (PrnP) that encodes native form of prion protein that is found in healthy animals (Figure 9.27) • Prion misfolding results in neurological symptoms of disease (e.g., resistance to proteases, insolubility, and aggregation) © 2015 Pearson Education, Inc. Neuronal cell Prnp Nucleus DNA Transcription Translation Normal function PrPc (normal prion) PrPSc-induced misfolding of PrPC Abnormal function PrPSc (misfolded prion) © 2015 Pearson Education, Inc. Figure 9.27 Chronic Wasting Disease in deer and elk Mad Cow Disease Kuru, KJD in humans © 2015 Pearson Education, Inc.