Viruses are fascinating microorganisms that hijack host cells to replicate. They employ various life cycles, from lytic to lysogenic, and use clever strategies to evade immune responses. Understanding viral replication is crucial for developing treatments and vaccines.

Viral infections can have profound impacts on host organisms. From causing direct cell damage to triggering autoimmune responses, viruses shape the health of individuals and populations. They even play a role in bacterial evolution through transduction, highlighting their ecological importance.

Viral Life Cycles and Replication

Lytic vs lysogenic cycles

• Lytic cycle involves virus entering host cell, replicating, and lysing the cell to release new virions occurs in virulent phages (T4 phage) and most animal viruses (influenza)
  • Steps include attachment, penetration, replication, assembly, and release
• Lysogenic cycle involves viral genome integrating into host cell's genome as a prophage host cell replicates normally, passing the prophage to daughter cells
  • Prophage can be induced to enter the lytic cycle under certain conditions (UV light, chemicals)
  • Occurs in temperate phages (lambda phage) and some animal viruses (herpes simplex virus)

Key steps in virus replication

1. Attachment: virus binds to specific receptors on the host cell surface (influenza hemagglutinin binds to sialic acid receptors)

2. Penetration: virus enters the cell via endocytosis or membrane fusion (HIV uses membrane fusion)

3. Uncoating: viral genome is released into the cytoplasm or nucleus (adenovirus uncoats in the nucleus)

4. Replication: viral genome is replicated using host cell machinery

   • DNA viruses typically replicate in the nucleus (herpes simplex virus)
   • RNA viruses typically replicate in the cytoplasm (poliovirus)

5. Assembly: new viral components are synthesized and assembled into virions (hepatitis B virus assembles in the cytoplasm)

6. Release: new virions are released from the host cell via lysis or budding (influenza buds from the cell membrane)

   • Viral shedding occurs during this stage, allowing for transmission to new hosts

Viral Structure and Host Interactions

• Viral envelope: lipid bilayer surrounding some viruses, derived from host cell membranes (influenza virus)
• Capsid: protein shell that encases the viral genome, providing protection and facilitating entry into host cells (adenovirus)
• Viral genome: genetic material of the virus, can be DNA or RNA (viral genome of hepatitis B virus is partially double-stranded DNA)
• Host cell receptor: specific molecule on the cell surface that viruses bind to for entry (host cell receptor ACE2 for SARS-CoV-2)
• Viral tropism: the ability of a virus to infect specific cell types or tissues, determined by the presence of appropriate receptors and cellular factors

Retroviruses vs latent viruses

• Retroviruses are RNA viruses that use reverse transcriptase to convert their RNA genome into DNA viral DNA integrates into the host cell's genome as a provirus
  • Provirus is transcribed and translated to produce new virions (HIV)
• Latent viruses have a viral genome that remains dormant within the host cell without causing apparent symptoms
  • Can reactivate and enter the lytic cycle under certain conditions like stress or immunosuppression (varicella-zoster virus causing shingles)
• Viral persistence: the ability of some viruses to remain in the host for extended periods, either through latency or chronic active infection (hepatitis B virus)

Human virus-host cell interactions

• Viruses exploit host cell receptors for attachment and entry (HIV uses CD4 and CCR5/CXCR4 receptors)
• Viruses hijack host cell machinery for replication and protein synthesis (influenza uses host cell ribosomes)
• Some viruses inhibit host cell protein synthesis to prioritize viral protein production (poliovirus)
• Viruses can evade or suppress the host immune response through various mechanisms
  • Antigenic drift and shift (influenza)
  • Inhibition of interferon production or signaling (Ebola virus)
  • Downregulation of MHC class I molecules (cytomegalovirus)

Transduction in gene transfer

• Transduction transfers genetic material from one bacterium to another via a virus (bacteriophage)
• Types of transduction
  • Generalized transduction: any bacterial DNA can be packaged into the phage capsid and transferred (P1 phage)
  • Specialized transduction: specific bacterial genes adjacent to the prophage are transferred (lambda phage)
• Contributes to the spread of antibiotic resistance (beta-lactamase genes) and virulence factors (toxin genes) among bacterial populations

Plant virus replication cycle

• Attachment: plant viruses often enter through wounds or insect vectors (aphids, whiteflies)
• Penetration: viruses move from cell to cell through plasmodesmata (tobacco mosaic virus)
• Replication occurs in the cytoplasm
  • Most plant viruses are RNA viruses and replicate in the cytoplasm (potato virus Y)
  • Some DNA plant viruses replicate in the nucleus (cauliflower mosaic virus)
• Assembly: new virions are assembled in the cytoplasm (brome mosaic virus)
• Release: virions are released by cell lysis or through plasmodesmata to neighboring cells (cucumber mosaic virus)
• Plant viruses do not typically undergo latent or lysogenic cycles

Host-Virus Interactions and Consequences

Human virus-host cell interactions

• Viruses can cause direct cytopathic effects, leading to cell damage or death
  • Cell lysis (adenovirus)
  • Syncytia formation (measles virus)
  • Inclusion bodies (rabies virus)
• Viruses can induce apoptosis (programmed cell death) or necrosis (premature cell death) in host cells
• Persistent infections can lead to chronic inflammation and tissue damage (hepatitis C virus)
• Viral infections can trigger autoimmune responses (Epstein-Barr virus and multiple sclerosis)
• Some viruses are oncogenic and can cause cellular transformation and cancer
  • Human papillomavirus (cervical cancer)
  • Hepatitis B and C viruses (liver cancer)
  • Epstein-Barr virus (Burkitt's lymphoma, nasopharyngeal carcinoma)

Transduction in gene transfer

• Transduction facilitates the evolution and adaptation of bacterial populations
  • Acquisition of new metabolic capabilities (lactose fermentation genes)
  • Development of antibiotic resistance (methicillin resistance in Staphylococcus aureus)
  • Enhanced virulence or survival mechanisms (Shiga toxin genes in E. coli)
• Transduction contributes to the genetic diversity and ecological success of bacteria