Viral Life Cycle

Viral Life Cycle

• The viral life cycle consists of attachment, penetration, uncoating, transcription, translation, genome replication, and assembly and release
• Initial infection is followed by an eclipse phase, where all viral particles disappear
• Viral genome takes over the host cell's protein-making machinery, directing the production of viral components

Attachment

• The interaction between a virus and its target cell begins with attachment to specific receptors on the cell
• Attachment is a critical step in target selection by many viruses
• Requires viral attachment protein and cellular receptors

Viral Attachment Proteins (VAP) and Receptors

• VAP binds to specific receptors on the target cell
• Examples of VAP and receptors:
  • Helper T-cell
  • Epithelial cell

Viral Penetration and Uncoating

• Enveloped viruses:
  • Fuse their envelope with the host cell membrane (e.g. Herpesvirus, Paramyxovirus, HIV)
  • Taken into the cell via endocytosis
• Non-enveloped viruses:
  • Penetrate host cells by various mechanisms, including direct penetration and endocytosis

Viral Replication

• Uncoating of the viral genome leads to the first step of viral replication, i.e., expression of mRNA (transcription)
• Translation of mRNA generates "early proteins" which often include synthesis of viral DNA or RNA polymerase and other proteins that play an important role in viral replication
• Viral genome replication leads to complementary strand synthesis and additional templates using nucleic acids

Viral Replication: Genome

• One convergent point for all viruses is that they all need to go through mRNA (+ve) strand synthesis to produce proteins
• Positive (+ve) nucleic acid (DNA or RNA) is the gene coding strand (or the actual gene sequence)
• Negative (-ve) nucleic acid (DNA or RNA) is the complementary strand to the gene coding mRNA (the template strand)

Viral Replication: Central Dogma of Biology

• Viral replication is a process of generating new genomes
• Special cases require specific viral enzymes:
  • RNA-dependent DNA polymerase (reverse transcriptase)
  • RNA-dependent RNA polymerase (RNA replicase)

Viral mRNA

• Viral mRNA can be processed with the same range of features that are found on eukaryotic RNA:
  • 5'-5' N7-methylguanosine-triphosphate CAP
  • Poly A tail (100-200 adenosine residues)
• Viruses can either make their own 5' CAP or possess a 3D RNA structure known as internal ribosomal entry site element (IRES)

Translation of Viral mRNA

• Different ways of producing viral proteins:
  • Transcription of individual mRNA molecules from the genome
  • Segmented genome where each molecule gives single mRNA
  • Production of a single long polyprotein that is later cleaved into individual functional peptides
  • Some viral genomes can be transcribed by "shifting the reading frame" with one or two nucleotides and thus produce different mRNA and proteins

Viral Assembly and Release

• Newly formed virion can be released by different means:
  • Budding causes the viral capsid to grab cellular membrane in a form of an envelope which is laced with viral proteins
  • Cell lyses caused by lytic viruses

Bacteriophage: Life Cycle

• Two possible existing bacteriophages:
  • Virulent (lytic) phage kills the host following infection
  • Lysogenic (temperate) phage undergoes lysogeny wherein the phage genome becomes a prophage (provirus) either by integration into the host chromosome or exist as an independent entity but replicating with the rate equal to the host genome multiplication

Viral Hosts and Tropism

• Viral tropism is the ability of a virus to infect a particular cell (cellular tropism), tissue (tissue tropism), or host species (host tropism)
• Tropism is defined by few factors:
  • Viral glycoproteins (VAP) integrated in the outer coat that target receptors on the surface of the host cells (susceptibility)
  • Presence of transcription factors allowing expression of viral genes
  • Presence of cell enzyme pathways to produce viral proteins is known as "permissivity"

Virus Groups by Transmission

• Enteric viruses: Fecal-oral route (e.g. Enteroviruses, Rotaviruses)
• Respiratory viruses: Droplets/aerosol (e.g. Influenza, Rhinoviruses, Measles)
• Zoonotic viruses: Vectors (such as arthropods) or animal to human (e.g. Rabies, Influenza A, Flaviviruses)
• Sexually transmitted viruses: Sexual contact (e.g. Herpes simplex, HIV, HPV)
• Vertically transmitted viruses: Maternal-neonatal transmission (e.g. Rubella, CMV, HIV, HSV)

Viral Infection: Outcomes

• Viral infection can have different outcomes, including:
  • Acute: Common cold, SARS
  • Acute with late complications: Measles
  • Latent-recurrent: HSV, VZV
  • Chronic: HBV, HCV
  • Chronic with late disease: HIV
  • Slow: JCV, Prions

This quiz covers the life cycle of viruses, including early enzymes, nucleic acid synthesis, and other stages. Adapted from Dr. Achut Malur's lectures and referencing Jawetz, Melnick & Adelberg's Medical Microbiology and Medical Microbiology by Murray et al.