I. Viral Genomes

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

Figure 9.1 Comparative genomics.

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

Class I & VII Class II Class III Class IV Class V Class VI dsDNA (±) virus ssDNA (+) virus dsRNA (±) virus ssRNA (+) virus ssRNA (–) virus 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 (replicative form) dsDNA intermediate Transcription mRNA (+) Transcription of the minus strand DNA Viruses RNA Viruses Class I classical semiconservative Class II classical semiconservative, discard (–) strand Class VII transcription followed by reverse transcription Class III make ssRNA (+) and transcribe from this to give ssRNA (–) complementary strand Class IV make ssRNA (–) and transcribe from this to give ssRNA (+) genome Class V make ssRNA (+) and transcribe from this to give ssRNA (–) genome Class VI make ssRNA (+) genome by transcription of (–) strand of dsDNA Genome replication Figure 9.2 The Baltimore classification of viral genomes. Figure 9.2

II. Viruses with DNA Genomes 9.6 Uniquely Replicating DNA Animal Viruses 9.7 DNA Tumor Viruses

9.6 Uniquely Replicating DNA Animal Viruses Double-stranded DNA animal viruses that have unusual replication strategies Pox viruses Adenoviruses

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

Viruses that replicate in The cytoplasm Pox viruses are ds DNA Viruses that replicate in The cytoplasm Figure 9.11 Smallpox virus. What do they need to do this?

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

Figure 9.12 Figure 9.12 Adenoviruses. Terminal protein Adenovirus DNA 5′ C + 3′ 3′ – C 5′ Plus strand is copied. 5′ C + 3′ 3′ – – C 5′ New synthesis leading strand C 5′ 5′ C + 3′ – C 5′ 3′ – C 5′ Direction of cyclization 3′ – C 5′ Minus strand cyclizes via inverted terminal repeats. Figure 9.12 Adenoviruses. – 5′ C 3′ Minus strand is copied. – New synthesis leading strand 5′ C 5′ C + 3′ Completed linear double strand 5′ C + 3′ 3′ – C 5′ Figure 9.12

Covalently linked protein TP pTP is primer Strand displacement replication Viral proteins

9.7 DNA Tumor Viruses Some DNA viruses can induce cancer (“tumor viruses or “oncoviruses” Human Papilloma Viruses (HPV) Herpesviruses

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

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

Figure 9.13b Infection + Viral DNA integrates into host DNA. Viral DNA Tumor virus DNA + Host DNA Viral DNA integrates into host DNA. Viral DNA Transcription of tumor-inducing genes Tumor virus mRNA Transport of mRNA to cytoplasm and translation Figure 9.13b Polyomaviruses and tumor induction. Viral tumor-induction proteins 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

9.7 DNA Tumor Viruses Some Herpesviruses cause cancer Epstein-Barr Virus HHV-8 Diverse mechanisms

III. Viruses with RNA Genomes 9.11 Viruses That Use Reverse Transcriptase

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

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”

RNA tumor virus genome Src is an “oncogene” C-src = normal cellular version V-src = version carried by virus

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)

IV. Subviral Agents 9.12 Viroids 9.13 Prions

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

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)

Figure 9.27 Figure 9.27 Prions. Neuronal cell Prnp Nucleus DNA Transcription Translation Normal function Figure 9.27 Prions. PrPc (normal prion) PrPSc-induced misfolding of PrPC Abnormal function PrPSc (misfolded prion) Figure 9.27

Chronic Wasting Disease in deer and elk Mad Cow Disease Kuru, KJD in humans