• Definition
    • Viruses are obligate intracellular parasites, meaning they require a host cell’s machinery to replicate.
    • A complete infectious virus particle is called a virion.
  • Structure & Classification
    • Genome: Can be DNA or RNA, which can be double-stranded (ds) or single-stranded (ss), and linear or circular. All viruses are haploid (one copy of the genome), except for retroviruses, which are diploid.
    • Capsid: A protein coat that encloses the viral genome. The capsid plus the genome is the nucleocapsid.
      • Icosahedral: A complex, spherical-appearing structure.
      • Helical: A spiral arrangement of proteins.
    • Envelope: A lipid bilayer derived from the host cell membrane that surrounds the capsid in some viruses (enveloped viruses). Those without it are called naked viruses.
      • Enveloped viruses are sensitive to alcohol, detergents, and ether.
    • General Rules & Exceptions:
      • All DNA viruses are dsDNA, except for Parvoviridae (ssDNA).
      • All DNA viruses replicate in the nucleus, except for Poxviridae (replicates in the cytoplasm).
        • It’s a massive, complex virus. It’s so large that it encodes its own DNA-dependent RNA polymerase and other replication machinery. It’s self-sufficient and doesn’t need to enter the nucleus.
      • All RNA viruses are ssRNA, except for Reoviridae (dsRNA).
      • Most RNA viruses replicate in the cytoplasm, except for Orthomyxoviridae (Influenza virus) and Retroviridae, which replicate in the nucleus.
        • Why Influenza? It has a segmented genome and uses a unique mechanism called “cap-snatching,” where it steals the 5’ caps from host pre-mRNAs in the nucleus to use as primers for its own mRNA synthesis.
  • Viral Replication Cycle
    1. Attachment: Virus binds to specific receptors on the host cell surface, which determines viral tropism (the type of cells a virus can infect).
    2. Penetration: The virus enters the host cell, often through endocytosis or fusion of the viral envelope with the cell membrane.
    3. Uncoating: The viral capsid is degraded, releasing the nucleic acid into the host cell.
    4. Synthesis: The virus hijacks host machinery to replicate its genome and synthesize viral proteins.
      • Positive-sense (+ssRNA) viruses: Their genome can be directly translated by host ribosomes, similar to mRNA.
      • Negative-sense (-ssRNA) viruses: Must carry their own RNA-dependent RNA polymerase to transcribe their genome into a positive-sense strand before protein synthesis can occur.
      • Retroviruses (e.g., HIV): Use a viral reverse transcriptase (an RNA-dependent DNA polymerase) to convert their RNA genome into DNA, which is then integrated into the host genome.
    5. Assembly: New viral components are assembled into progeny virions.
    6. Release: New viruses exit the host cell.
      • Naked viruses are typically released through cell lysis.
      • Enveloped viruses are released via budding, acquiring their envelope from the host cell membrane.
  • Viral Genetics
    • Recombination: Exchange of genetic material between two homologous viral genomes.
    • Reassortment: The mixing of genome segments when a host cell is co-infected with two segmented viruses (e.g., Influenza virus, Rotavirus). This can lead to sudden, major changes known as antigenic shift, which can cause pandemics.
    • Genetic Drift: Minor changes due to point mutations in the viral genome over time (e.g., seen in influenza).
    • Complementation: When one of two viruses infecting a cell has a mutation that results in a non-functional protein, the other virus can “complement” it by making a functional version of that protein, allowing both viruses to replicate.
    • Phenotypic Mixing: Progeny virions contain the genome of one virus but are coated with surface proteins from another virus that co-infected the cell. The next generation of viruses will revert to their original phenotype, as the genome is unchanged.
  • Laboratory Diagnosis
    • Nucleic Acid Amplification Tests (NAATs): Techniques like PCR are highly sensitive and specific for detecting viral DNA or RNA. “Viral load” quantification is crucial for managing infections like HIV and HCV.
    • Antigen Detection: Direct detection of viral proteins in clinical samples using methods like ELISA or immunofluorescence. Faster but less sensitive than NAATs.
    • Serology: Detects host antibodies (IgM or IgG) against the virus. An IgM response suggests a recent or acute infection, while IgG indicates a past infection or vaccination.
    • Viral Culture: Growing the virus in cell lines, which can cause visible changes known as cytopathic effects (CPE). Historically the gold standard but slow.