Chapter Summary


  • The phage T4 virion consists of a head containing its DNA genome and accessory proteins, a tail composed of an internal tube with a sheath; and tail fibers.
  • T4 is adsorbed by binding of the tail fibers to bacterial outer membrane receptors, followed by binding of the tail baseplate.
  • Injection of T4 DNA through the internal tube leads to lytic infection. Early genes encode a DNA polymerase and a DNase to cleave host DNA.
  • Rolling-circle replication generates progeny genomes linked in a concatemer. The concatemer is cut with an offset, so that each linear genome has a slight overlap, cut at a different position in the sequence.
  • Virions are self-assembled, including packaging of DNA into the head, in arrays beneath the inner membrane.
  • Cell lysis is caused by a lysozyme expressed by late genes in the T4 genome.
  • The phage T4 assembly process was dissected in studies of temperature-sensitive mutants and nonsense mutants with suppressor tRNA. This strategy of genetic dissection was used as a model for experiments on animal development.


  • Poliovirus, a picornavirus, is icosahedral. Its genome consists of single-stranded (+) strand RNA.
  • Polio virions attach to poliovirus receptors (PVRs). Conformational change in the capsid allows DNA insertion for uncoating in the cytoplasm.
  • Poliovirus RNA is replicated within ER-derived vesicles by RNA-dependent RNA polymerase. Genome replication is primed by virus-encoded protein primer 3AB, which is cleaved to 3B (VPg).
  • (+) strand RNA serves as a template for (–) strand RNA. The (–) strand RNA then serves as template for (+) strand RNA, which is either translated to proteins or encapsidated into progeny virions.
  • RNA for polio gene expression is exported to the cytoplasm for translation by host ribosomes. Virions are packaged in the cytoplasm and exported by an unknown mechanism.
  • Poliovirus enters the body through the gastrointestinal tract. In severe cases, the virus disseminates through the lymph and blood, crossing the blood-brain barrier to infect neurons and cause paralysis.


  • Influenza virus causes periodic pandemics of respiratory disease. New virulent strains arise through recombination of human and avian strains.
  • The influenza virus consists of segmented (–) strand RNA. Each segment is packaged with nucleocapsid proteins. Segments from different strains recombine through coinfection.
  • Capsid and matrix proteins enclose the RNA segments of the influenza virus. The matrix is enclosed by an envelope containing spike proteins.
  • Envelope proteins mediate virion attachment. The envelope proteins include a fusion peptide that undergoes conformational change to cause fusion between viral envelope and host cell membrane. For influenza, the virion is internalized by endocytosis.
  • Lysosome fusion with endosomes triggers viral envelope fusion with the endosome membrane. The viral genome and proteins are then released into the cytoplasm. Viral (–) strand RNA segments are uncoated and enter the nucleus.
  • Influenza mRNA synthesis is primed by capped RNA fragments, cleaved from host mRNA. The viral mRNAs return to the cytoplasm for translation.
  • Genomic RNA synthesis is primed by the nucleocapsid protein (NP). First, (+) strand RNA is synthesized as a template for (–) RNA strands, which are then packaged in newly made nucleocapsid protein and exported to the cytoplasm.
  • Envelope proteins of influenza virus are synthesized at the ER for transport to the cell membrane.
  • Influenza virus is assembled at the cell membrane, where capsid, matrix, and (–) strand RNA components are packaged into envelope.


  • Human immunodeficiency virus (HIV) causes an ongoing epidemic of acquired immunodefi- ciency syndrome (AIDS). There is no cure, but molecular biology has led to drugs that extend life expectancy.
  • HIV is a retrovirus whose RNA genome is reversetranscribed into double-stranded DNA, which integrates into the DNA of the host cell.
  • The HIV core particle contains two copies of its RNA genome, each bound to a primer (host tRNA) and reverse transcriptase (RT). The core is surrounded by an envelope containing spike proteins.
  • HIV binds the CD4 receptor of T lymphocytes together with the chemokine receptor CCR5. Following virion-receptor binding and envelopemembrane fusion, HIV virions are released into the cytoplasm.
  • DNA is synthesized in the nucleus from the retroviral RNA, primed by the tRNA, and synthesized by reverse transcriptase. RNA degradation allows formation of a double-stranded DNA. The retroviral DNA integrates into the host genome.
  • Retroviral mRNAs are exported to the cytoplasm for translation. Envelope proteins are translated at the ER and exported to the cell membrane.
  • Retroviruses are assembled at the cell membrane, where virions are released slowly, without lysis. Alternatively, the accumulation of retroviral proteins in the cell membrane leads to cell fusion, forming syncytia.
  • Accessory proteins regulate virion formation and the latent phase, in which double-stranded DNA persists without reproduction of progeny virions.
  • Ancient retroviral sequences persist within animal genomes, including the human genome.


  • Herpes simplex virus causes recurring eruptions of sores in the oral or genital mucosa. Initial transmission is by oral or genital contact, followed by eruptions from reactivated virus latent in ganglial neurons.
  • The herpes virion contains a double-stranded DNA genome, packed in an icosahedral capsid. The capsid is surrounded by numerous matrix proteins and by an envelope.
  • HSV attachment may involve several alternative receptors. A microtubular scaffold transports the herpes virions to the nucleus, where the DNA genome is inserted. The DNA circularizes for transcription.
  • DNA genomes of HSV are synthesized by the rolling-circle method, using viral DNA polymerase supplemented by viral and host-generated components.
  • Infectious mRNA expression leads to production of capsid, matrix, and envelope proteins for assembly of HSV. Alternatively, LAT protein expression leads to latent infection, usually in nerve cells, where the DNA persists silently for months or years.
  • HSV assembly occurs at the nuclear membrane or other membranes. The virions are released from the cell by exocytosis. Rapid release leads to mucosal pathology.


  • Gene transfer vectors are made from viruses.
  • Virulence genes are deleted, and efficient promoter sequences from other viruses are inserted.
  • Adenoviral vectors circularize and replicate separately from the host genome.
  • Lentiviral vectors integrate within the host genome.