Introduction to Virology: Characteristics, Classification, and Life Cycles

Significance and Impact of Viruses * Viral Mortality Statistics: Viruses are responsible for immense global mortality. It is estimated that almost $27 imes 10^6$ (27 million) people have died worldwide, with almost $1.2 imes 10^6$ (1.2 million) deaths in the United States alone. * Pandemic History: Excluding cholera, every major pandemic since the year $1900$ has been caused by a virus. * Ubiquity and Ecology: Viruses are found everywhere on the planet. It is estimated that there are $10^{31}$ viruses globally. The majority of these viruses infect prokaryotes. * Evolutionary Impact: Viruses have fundamentally shaped life. Approximately $8\%$ of the human genome is viral in origin. * Viruses as Tools: Beyond disease, viruses are used in biotechnology for: * Vaccines. * Gene transfer (gene therapy). * Phage therapy: Using viruses to kill pathogenic bacteria. # General Characteristics and Architecture of Viruses * Core Definition: Viruses are obligate intracellular parasites. They are genetic information (DNA or RNA) contained within a protective coat. * States of Existence: Viruses are infectious agents, not organisms. They are inert particles outside a host, possessing no metabolism, replication capability, or motility of their own. * Basic Components: * Genetic Material: Either DNA or RNA, but never both. Genomes can be linear or circular, and double-stranded ($ds$) or single-stranded ($ss$). * Capsid: A protein coat that protects the nucleic acids. It is composed of identical subunits called capsomeres. * Nucleocapsid: The complex formed by the capsid plus the nucleic acids it contains. * Envelope (Optional): Some viruses are enveloped, meaning the nucleocapsid is enclosed within a lipid bilayer membrane derived from the host. Enveloped viruses often have matrix protein located between the nucleocapsid and the envelope. * Naked Viruses: Viruses lacking an envelope are referred to as non-enveloped or naked viruses. These are generally more resistant to disinfectants. * Size Variance: * Smallest: Approximately $10\,nm$ with about $10$ genes. * Largest: Approximately $800\,nm$. * Typical: Tens of $nm$ in size with a handful to a few hundred genes. * Attachment Mechanisms: * Bacteriophages: Use tail fibers for attachment. * Animal Viruses: Frequently use spikes (protein projections) to attach to specific host receptor sites. * General Shapes: 1. Icosahedral: A polyhedron with $20$ faces. 2. Helical: Spiral/cylindrical structure. 3. Complex: Any shape that does not fit into the icosahedral or helical categories. # Viral Classification and Nomenclature * Baltimore Classification: A primary system for classifying viruses based on how they produce mRNA and replicate their genomes. * Suffixes in Naming: * Family: Ends in the suffix $-viridae$ (e.g., Coronaviridae). * Genus: Ends in the suffix $-virus$ (e.g., Enterovirus). * Naming Conventions: There is no single consistent pattern. * Appearance: Coronaviridae is named after "corona," meaning crown. * Geography: Bunyaviridae is named after Bunyamwera, Uganda; Norovirus is named after Norwalk, Ohio. * Disease: Species names often reflect the disease they cause (e.g., poliovirus causes poliomyelitis). # Bacteriophage Life Cycles * General Types: 1. Lytic Phages: Always lead to a lytic (cell-bursting) infection cycle. 2. Temperate Phages: Can choose between a lytic cycle or a lysogenic (latent) cycle. 3. Filamentous Phages: (Covered in independent reading). * Lytic Cycle (Model: T4 Phage): The T4 phage is a $dsDNA$ virus approximately $90\,nm$ wide and $200\,nm$ long, encoding $289$ proteins. 1. Attachment: Binds to $\text{OmpC}$ porin proteins and Lipopolysaccharide ($\text{LPS}$) on Escherichia coli. 2. Genome Entry: Tail contracts and injects DNA; the phage coat remains outside. 3. Synthesis: Host gene expression is turned off; host DNA is broken down for supplies; viral DNA is replicated and virion components are synthesized. 4. Assembly: Structural and assembly proteins are made and assembled into virions. 5. Release: Host cell is lysed. The average burst size is $\approx 130$ phages. The entire process takes approximately $30\, ext{minutes}$. * Lysogenic Cycle (Model: Lambda $[\lambda]$ Phage): * Prophage: The integrated viral DNA. * Lysogen: The infected bacterial cell. * Integration: Viral DNA integrates into the host genome and is copied during cell division. * Excision: The prophage can be excised to enter the lytic cycle, occurring roughly once per $1/10,000$ divisions in high-nutrient conditions. * Lysogenic Conversion: The prophage changes the host phenotype (e.g., encoding toxins like those in certain S. aureus strains). * Immunity to Superinfection: The repressor maintaining the prophage also prevents gene expression from incoming identical phage DNA. # Bacterial Defenses against Phages * Preventing Attachment: Bacteria alter/cover receptors via: * Loss of the receptor entirely. * Proximity-masking: Staphylococcus aureus produces Protein A to mask receptors. * Barriers: Capsules, slime layers, and biofilms. * Restriction-Modification Systems: Requires two enzymes: 1. Restriction Enzymes: Cut specific, short DNA sequences (restriction sites). 2. Modification Enzymes: Methylate host DNA at restriction sites so the restriction enzyme cannot cut "self" DNA. If unmethylated phage DNA enters, it is degraded. Occasionally, the phage is methylated first and survives. * CRISPR System: Clusters of Regularly Interspersed Short Palindromic Repeats. 1. Record of Infection: Phage spacer DNA is inserted into the CRISPR array. 2. RNA Binding: Spacer DNA is transcribed and cut into small RNAs that bind to $\text{Cas}$ (CRISPR associated sequences) proteins. 3. Targeting: The spacer RNA binds to matching incoming phage genomes, targeting them for destruction. # Animal Virus Five-Step Infection Cycle * 1. Attachment: Viruses bind to receptors (usually glycoproteins) on the cytoplasmic membrane. This determines tropism (host/tissue range). * 2. Penetration and Uncoating: * Fusion: Enveloped viruses fuse their envelope with the host membrane. * Endocytosis: Membrane surrounds the virion to form a vesicle. * Uncoating: Nucleic acid separates from the protein capsid. * 3. Synthesis: * Includes expression of viral structural/catalytic genes and genome replication. * Most DNA viruses replicate in the nucleus. * 4. Assembly: Capsids form; genomes and enzymes are packaged. This occurs in the nucleus or cytoplasm organelles. * 5. Release: * Budding: Enveloped viruses push through the membrane, picking up the lipid bilayer and matrix proteins. * Lysis: Non-enveloped viruses are released when the host cell dies, often via apoptosis. # Strategies for Viral Genome Replication * DNA Viruses: Usually replicate in the nucleus. They use DNA-dependent DNA polymerase (typically host-derived) and DNA-dependent RNA polymerase (transcriptase) for mRNA. Poxviruses are an exception, replicating in the cytoplasm with their own enzymes. * RNA Viruses: Most replicate in the cytoplasm and are single-stranded. They require a virally encoded Replicase (RNA-dependent RNA polymerase). * $ss(+)RNA$: Used directly as mRNA. * $ss(-)RNA$ and $dsRNA$: Must carry the replicase enzyme within the virion because the host cannot translate/use these forms directly. * Antigenic Drift: Caused by the replicase's lack of proofreading. * Retroviruses: Use Reverse Transcriptase (RNA-dependent DNA polymerase) to make DNA from an RNA template. Once integrated into the host genome, the virus cannot be eliminated. # Baltimore Classification Matrix * Type I: $dsDNA$; uses host transcriptase for mRNA and host machinery for genome. * Type II: $ssDNA$; uses host machinery to make $dsDNA$, then host transcriptase for mRNA. * Type III: $dsRNA$; uses viral $\text{RDRP}$ to make $+mRNA$ and $-RNA$ genome halves. * Type IV: $ss(+)RNA$; uses viral $\text{RDRP}$ to make $-RNA$ template and then $+mRNA$ genomes. * Type V: $ss(-)RNA$; uses viral $\text{RDRP}$ to make $+mRNA$ and then $-RNA$ genomes. * Type VI: $ss(+)RNA$ (Retrovirus); uses viral reverse transcriptase to make $-DNA$, then host machinery to make $dsDNA$.