Viral Infections: Persistence, Latency, and Immune Evasion

Posted on Jan 7, 2026 in Biology

1. Defective-Interfering Particles and Persistent Infections

Defective-interfering (DI) particles compete with standard viruses for replication machinery and suppress productive infection. This decreases viral output, avoids complete cell destruction, and sustains infection at low intensity.

2. Viral Nucleic Acid Sensing by Pattern Recognition Receptors (PRRs)

Two PRR Classes Sensing Viral Nucleic Acids:

  • RIG-I–like Receptors (RLRs): Recognize viral double-stranded RNA (dsRNA) present in the cytoplasm.
  • Toll-like Receptors (TLRs): Specifically TLR3, TLR7, and TLR9 identify dsRNA, single-stranded RNA (ssRNA), and unmethylated CpG DNA within endosomal compartments.

3. Reasons for Lifelong HIV Infection

HIV infection remains lifelong due to:

  1. HIV inserts its DNA into host chromosomes, creating a stable provirus.
  2. Ongoing viraemia persists because the virus replicates at low levels and establishes durable infection in bone marrow–derived cells.

4. Determinants of Acute, Latent, or Persistent Viral Infection

The outcome is influenced by:
  • Viral Traits: Gene activity, apoptosis inhibition, and replication capacity.
  • Host Cell Traits: Cell type, immune defenses, and receptor availability.

5. Comparing EBV Episomal Latency with $\lambda$ Phage Integrated Latency

  • Epstein-Barr Virus (EBV): DNA stays episomal (circular, non-integrated), maintained by the EBNA-1 protein.
  • Bacteriophage $\lambda$: DNA becomes integrated into the bacterial genome via Int-driven recombination.

6. Latency and Persistence Comparison in $\lambda$ Phage, EBV, and HIV

  • $\lambda$ Phage: Decides between lytic and lysogenic states depending on cII stability. Lysogeny occurs when $\lambda$ DNA inserts into the bacterial genome via Int. Reactivation happens when UV or SOS signals eliminate the cI repressor.
  • EBV: Maintains latency in B cells with DNA in episomal form. EBNA-1 preserves the episome, while LMPs promote B-cell growth.
  • HIV: Does not enter latency but stays persistently active since its DNA integrates permanently into host chromosomes, producing lifelong low-level viraemia.

7. Viral Cytopathology and Immune Influence on Outcomes

Viral Damage Mechanisms:

Viral damage includes blocking host transcription (rhabdoviruses), displacing host mRNA, inability to start translation, mRNA breakdown (influenza), apoptosis, and ionic disruption.

Immune System Influence:

Immune responses like interferons can suppress viral replication, resulting in persistence rather than cell death. Certain viruses (e.g., HCMV UL37x1) inhibit apoptosis to sustain long-term infection.

8. Transmission Routes and Immunity Shaping Viral Spread

  • Respiratory Viruses: Spread broadly due to frequent exposure; innate defenses include mucosal barriers.
  • Fecal–Oral Viruses: Must resist stomach acid (e.g., rotavirus).
  • Vector-Borne Viruses: Bypass defenses by entering through insect bites.
  • Sexual and Vertical Transmission: Involve mucosal or blood contact.

Epidemiology is influenced by $\text{MID}_{50}$ and $\text{R}_0$, which determine viral contagiousness.

9. Viral Oncogenesis Mechanisms and Host Factors

Viral Interference with Cell-Cycle Regulation:

Oncogenic viruses interfere with cell-cycle regulation:

  • HPV E6/E7, SV40 large T, adenovirus E1A disable Rb or p53.
  • Viral DNA may integrate or persist during latency.

Host influences—age, genetics, diet, and carcinogen exposure—also play roles. Most viruses avoid killing the host cell, enabling survival and accumulation of mutations.