Latency in DNA Viruses: Key Points on HSV

Latency in a DNA Virus: Herpes Simplex Virus (HSV)

• Disease Overview:

  • HSV-1: Causes cold sores; 85-99% global adult infection.

  • HSV-2: Causes genital ulcers; 10-60% global adult infection.

  • Neonatal HSV: Transmitted at birth; can cause encephalitis and death; risk factors include maternal poverty.

• Pathogenesis:

  • Lytic infection in epithelial cells leads to cell death and immune response, causing sores.

  • Virus infects sensory neurons, remaining latent until immune compromise triggers reactivation.

  • Nerve latency: Trigeminal nerve in face, sciatic nerve in groin.

• HSV-1 Genome:

  • ~150 kb episome; approximately 80+ genes.

  • Microarrays used to determine gene activation in neurons vs epithelial cells.

• Microarray Methodology:

  • Gene sequences printed on chips, cDNA labeled with fluorescent dyes collected from infected cells at different times.

  • Competitive binding to the chip detects gene expression levels.

  • Results indicate immediate early (alpha), early (beta), and late (gamma) gene categories.

  • Only LAT transcripts present during latency suppress alpha genes.

• Alpha Genes in Lytic Cycle:

  • Function determined via knock-out or knock-down (RNAi) methods.

  • Alpha gene product αTIF required for activation of other alpha genes.

• Alpha Gene Functions:

  • ICP27: Inhibits mRNA splicing, enhancing resources for viral translation.

  • ICP47: Immune evasion via MHCI inhibition.

  • ICP0, ICP4: Serve as transcription factors for beta genes.

• Other Herpes Viruses:

  • VZV: Lytic in epidermal cells, latent in sensory neurons (chicken pox/shingles).

  • EBV: Lytic in epithelial cells, latent in B cells (mononucleosis, lymphomas).

  • CMV: Lytic in epithelial cells, possibly latent in white blood cells.

Research Implications

• Exploring how HSV identifies its location in neurons.

• Investigating functions of alpha genes during the viral lytic cycle.