Premed · Premed · General Biology 1

Lecture 27: Viruses and Viral Genetics

General Biology I — Molecular & Cellular

Learning Objectives

By the end of this lecture, students will be able to:

1. Describe the general structure and classification of viruses
2. Compare and contrast the lytic and lysogenic bacteriophage life cycles
3. Explain the replication strategies of DNA viruses, RNA viruses, and retroviruses
4. Describe how viruses cause disease and the mechanisms of viral pathogenesis
5. Explain the roles of viruses in gene transfer and their applications in biotechnology

Lecture Content

I. General Properties of Viruses

Viruses are obligate intracellular parasites — they cannot replicate independently; they must infect a host cell and hijack its machinery. Viruses are not considered living organisms by most definitions because they: Lack their own metabolism (no ATP generation, no ribosomes) Cannot reproduce independently. Do not maintain homeostasis. However, viruses evolve through mutation and natural selection, and they contain genetic material. Size: typically 20-300 nm — much smaller than most bacteria; visible only by electron microscopy. Exceptions: giant viruses (Mimivirus, ~750 nm; Pandoravirus, ~1000 nm).

Viral Structure

Nucleic acid genome — can be: DNA or RNA (never both) Double-stranded (ds) or single-stranded (ss) Linear or circular. Segmented or non-segmented. Capsid — a protein shell that encloses the genome. Composed of protein subunits called capsomeres (made of one or more types of proteins) The capsid + genome = nucleocapsid. Capsid morphology:. Icosahedral — 20-sided symmetry; roughly spherical (e.g., adenovirus, poliovirus) Helical — rod-shaped; capsomeres arranged in a spiral around the nucleic acid (e.g., tobacco mosaic virus, Ebola) Complex — irregular shapes; bacteriophages (e.g., T4 phage with head, tail, tail fibers, and baseplate) Envelope — some viruses are surrounded by a lipid bilayer derived from the host cell membrane. Contains viral glycoproteins (spikes) that mediate attachment to host cells. Enveloped viruses — influenza, HIV, SARS-CoV-2, herpes. Non-enveloped (naked) viruses — adenovirus, poliovirus, norovirus. Enveloped viruses are more sensitive to detergents, desiccation, and heat (the envelope is fragile).

<image>A multi-panel figure showing three major types of viral morphology. Panel A (Icosahedral virus): An adenovirus is shown as a 20-sided polyhedron with triangular capsomere faces, fiber proteins projecting from each vertex with knob-shaped attachment proteins at their tips. A cutaway reveals the linear dsDNA genome inside. Panel B (Helical virus): Tobacco mosaic virus is shown as a rigid rod with capsomere proteins arranged in a helix around a central ssRNA genome. A cross-section shows the RNA nestled in a groove between protein subunits. Panel C (Complex virus — bacteriophage T4): The phage has an icosahedral head (containing linear dsDNA), a helical tail tube surrounded by a contractile tail sheath, a baseplate with tail pins, and six long tail fibers extending outward for attachment to the bacterial surface.</image>

II. Viral Classification

Baltimore classification (David Baltimore, Nobel Laureate) — classifies viruses into seven groups based on their genome type and replication strategy:

(+) sense RNA — can be directly translated by ribosomes (acts as mRNA) (-) sense RNA — complementary to mRNA; must first be transcribed to (+) sense by an RNA-dependent RNA polymerase (RdRp) that the virus brings with it.

III. Bacteriophage Life Cycles

The Lytic Cycle

The phage replicates rapidly and destroys (lyses) the host cell. Steps (using T4 phage as a model): Attachment (adsorption) — tail fibers bind to specific receptors on the bacterial surface. Penetration (injection) — the tail sheath contracts, and the phage injects its DNA through the cell wall; the capsid remains outside. Biosynthesis — phage DNA takes over the host cell: Host DNA is degraded. Phage genes are transcribed and translated using host machinery. Phage DNA is replicated. Capsid proteins and other structural components are synthesized. Assembly (maturation) — new phage particles are assembled (DNA is packaged into capsid heads, tails are attached) Lysis and release — phage-encoded lysozyme degrades the bacterial cell wall; the cell bursts, releasing ~100-200 new phage particles (burst size) Phages that only undergo the lytic cycle are called virulent phages (e.g., T4).

The Lysogenic Cycle

The phage DNA integrates into the host chromosome and replicates passively with it — no immediate lysis. Steps (using bacteriophage lambda as a model): Attachment and injection (same as lytic) Integration — phage DNA circularizes and integrates into the bacterial chromosome by site-specific recombination (at the att sites) The integrated phage DNA is called a prophage. The bacterium carrying a prophage is called a lysogen. Replication as part of the host genome — the prophage is replicated along with the bacterial chromosome every time the cell divides; all daughter cells carry the prophage. The prophage is maintained in a dormant state by the lambda repressor (cI protein), which prevents expression of lytic genes. Induction — under stress conditions (UV radiation, DNA damage, nutrient depletion), the SOS response triggers cleavage of the lambda repressor by RecA. The prophage excises from the chromosome and enters the lytic cycle. Phages capable of both lytic and lysogenic cycles are called temperate phages (e.g., lambda).

Lysogenic conversion — the prophage may carry genes that alter the host phenotype: Corynebacterium diphtheriae — diphtheria toxin gene is carried by a prophage; Vibrio cholerae — cholera toxin gene is carried by phage CTXphi; Clostridium botulinum — botulinum toxin gene on a prophage.

<image>A diagram comparing the lytic and lysogenic cycles of a temperate bacteriophage. Starting at the top, a phage attaches to a bacterium and injects its DNA. The pathway then branches. Left path (Lytic cycle): Phage DNA circularizes, host DNA is degraded, phage DNA replicates, new phage components are synthesized, phage particles are assembled, and the cell lyses releasing ~100 new phages. Right path (Lysogenic cycle): Phage DNA integrates into the bacterial chromosome at the att site to become a prophage. The lysogenic bacterium divides normally, replicating the prophage with its own DNA. All daughter cells are lysogens. An arrow labeled "Induction (e.g., UV light, SOS response)" shows the prophage excising from the chromosome and entering the lytic cycle. The lambda repressor (cI) is shown maintaining lysogeny by repressing lytic gene expression, and RecA-mediated cleavage of cI is shown triggering induction.</image>

IV. Animal Virus Replication

General Steps

1. Attachment (adsorption) — viral surface proteins bind to specific host cell receptors

This determines host range and tissue tropism. Examples: HIV gp120 binds CD4 and CCR5/CXCR4; SARS-CoV-2 spike protein binds ACE2; influenza hemagglutinin binds sialic acid. Entry (penetration):. Enveloped viruses — enter by membrane fusion (envelope fuses with host plasma membrane or endosomal membrane) or receptor-mediated endocytosis. Non-enveloped viruses — enter by endocytosis or direct penetration. Uncoating — removal of the capsid to release the viral genome. Replication and gene expression — strategy depends on the Baltimore class (see above) Assembly — new viral particles are assembled in the cytoplasm or nucleus. Release:. Enveloped viruses — acquire their envelope by budding through the host cell membrane (plasma membrane, ER, or Golgi); may not immediately kill the cell. Non-enveloped viruses — typically released by cell lysis.

Retrovirus Life Cycle (HIV as a Model)

HIV (Human Immunodeficiency Virus) — a retrovirus (Baltimore Group VI) Genome: two copies of (+) ssRNA + reverse transcriptase enzyme inside the capsid. Replication cycle: Attachment — gp120 binds CD4 receptor on helper T cells (and macrophages); gp41 mediates fusion with the cell membrane after binding a co-receptor (CCR5 or CXCR4) Entry and uncoating — capsid enters the cytoplasm and disassembles. Reverse transcription — reverse transcriptase converts the ssRNA genome into double-stranded DNA (dsDNA). Reverse transcriptase is error-prone (no proofreading) — high mutation rate. Integration — the viral dsDNA (provirus) is transported to the nucleus and integrated into the host chromosome by integrase. The integrated provirus remains permanently in the host genome. Transcription — host RNA polymerase II transcribes the proviral DNA into mRNA and new genomic RNA. Translation — viral mRNAs are translated into viral proteins (including polyproteins that must be cleaved) Assembly — viral components assemble at the plasma membrane. Budding — new virus particles bud from the cell, acquiring a lipid envelope with gp120/gp41. Maturation — protease cleaves polyproteins into functional proteins; the mature virion is now infectious.

Antiretroviral drugs target multiple steps: NRTIs and NNRTIs — inhibit reverse transcriptase. Integrase inhibitors (e.g., raltegravir) — block integration. Protease inhibitors (e.g., ritonavir) — block polyprotein cleavage. Entry inhibitors (e.g., maraviroc blocks CCR5; enfuvirtide blocks gp41 fusion) HAART (Highly Active Antiretroviral Therapy) — combination of drugs from multiple classes.

V. Viral Genetics and Evolution

Sources of Genetic Variation in Viruses

Mutation:. RNA viruses have very high mutation rates (~10^-3 to 10^-5 per base per replication) because RNA-dependent RNA polymerase and reverse transcriptase lack proofreading. DNA viruses have lower mutation rates (closer to their host cells) High mutation rates generate enormous genetic diversity — viral quasispecies (populations of closely related but genetically distinct variants).

Recombination:. Exchange of genetic material between two viral genomes co-infecting the same cell. Common in DNA viruses and retroviruses (template switching by reverse transcriptase).

Reassortment:. Occurs in viruses with segmented genomes (e.g., influenza — 8 RNA segments) When two different strains co-infect the same cell, segments from both strains can be mixed into new progeny virions. Antigenic shift — a major, sudden change in surface antigens due to reassortment. Responsible for influenza pandemics (e.g., swine flu, avian flu) Antigenic drift — gradual accumulation of point mutations in surface antigens (hemagglutinin, neuraminidase) Responsible for seasonal flu epidemics.

<image>A two-panel figure on influenza viral evolution. Panel A (Antigenic drift): An influenza virus is shown with hemagglutinin (HA) and neuraminidase (NA) surface proteins. Over successive replication cycles, random point mutations accumulate in the HA gene, gradually altering the shape of the HA protein. Antibodies raised against the original strain progressively lose their ability to recognize the mutated HA. This explains why flu vaccines must be updated annually. Panel B (Antigenic shift / Reassortment): Two different influenza strains (e.g., a human strain with H1N1 segments and an avian strain with H5N1 segments) co-infect the same cell (such as a pig cell). During replication, the 8 RNA segments from both strains are mixed. A progeny virus emerges with a novel combination of segments (e.g., H5N1 surface proteins with human-adapted internal genes), creating a dramatically new strain against which the population has no pre-existing immunity — this can trigger a pandemic.</image>

VI. Viruses and Gene Transfer in Bacteria

Viruses facilitate horizontal gene transfer among bacteria:

Transduction

Transfer of bacterial DNA from one bacterium to another via a bacteriophage.

Generalized transduction: During the lytic cycle, host DNA is accidentally packaged into a phage capsid instead of phage DNA. When this defective phage infects a new bacterium, it injects the donor bacterial DNA. The donor DNA can be incorporated into the recipient's chromosome by homologous recombination. Any gene from the donor can be transferred (random).

Specialized transduction: Occurs during imprecise excision of a prophage from the host chromosome (lysogenic cycle) The excised DNA includes some phage DNA and some adjacent bacterial DNA. When the phage replicates and infects a new cell, it transfers the specific bacterial genes flanking the original integration site. Only genes near the prophage integration site can be transferred.

VII. Other Infectious Agents

Viroids

Smallest known pathogens — short, circular, single-stranded RNA molecules (~250-400 nucleotides) No capsid, no envelope, no protein-coding genes. Replicate in the host cell nucleus using host RNA polymerase. Cause diseases only in plants (e.g., potato spindle tuber viroid) May interfere with gene regulation through RNA silencing pathways.

Prions

Infectious protein particles — contain no nucleic acid at all. Composed of a misfolded form (PrP^Sc) of a normal cellular protein (PrP^C) PrP^Sc acts as a template that induces normal PrP^C to refold into the pathological conformation — a chain reaction. PrP^Sc aggregates form amyloid plaques in the brain, causing neurodegeneration. Cause transmissible spongiform encephalopathies (TSEs):. Creutzfeldt-Jakob disease (CJD) — humans. Bovine spongiform encephalopathy (BSE / mad cow disease) — cattle. Scrapie — sheep. Kuru — historically observed in Papua New Guinea (transmitted by ritualistic cannibalism) Extremely resistant to standard sterilization methods (heat, UV, chemical disinfectants) Discovery and characterization: Stanley Prusiner (1982) — Nobel Prize in 1997.

VIII. Viruses and Human Health

Oncogenic viruses (tumor viruses) — viruses that can cause cancer: HPV (Human Papillomavirus) — cervical cancer, oropharyngeal cancer (E6 and E7 oncoproteins inactivate p53 and Rb) Hepatitis B and C viruses — hepatocellular carcinoma. EBV (Epstein-Barr Virus) — Burkitt lymphoma, nasopharyngeal carcinoma. HTLV-1 — adult T-cell leukemia. HHV-8 — Kaposi sarcoma. Estimated that ~15-20% of human cancers have a viral etiology.

Emerging and re-emerging viruses:. Often arise through zoonotic spillover — transfer from animal reservoirs to humans. Examples: HIV (from chimpanzees), SARS-CoV-2 (likely bat origin), Ebola (fruit bats), Zika (mosquito-borne), influenza (birds and pigs) Factors driving emergence: deforestation, urbanization, global travel, climate change, agricultural practices.

Vaccines:. Live attenuated — weakened virus (e.g., MMR, oral polio) Inactivated — killed virus (e.g., inactivated polio, rabies) Subunit — purified viral proteins (e.g., hepatitis B surface antigen) mRNA vaccines — deliver mRNA encoding a viral protein (e.g., Pfizer-BioNTech and Moderna COVID-19 vaccines) Viral vector — a harmless virus delivers genes encoding antigens (e.g., AstraZeneca, J&J COVID-19 vaccines).

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