Viruses: Herpes, HIV, and Influenza

Overview of Viruses

  • Types of Viruses
  • dsDNA virus (Herpes)
    • Disease caused: Herpes infections
    • Entry, replication, and exit mechanisms
  • (+) Strand RNA Virus (HIV)
    • Disease caused: HIV/AIDS
    • Entry, replication, and exit mechanisms
  • (-) Strand RNA virus (Influenza)
    • Disease caused: Influenza
    • Entry, replication, and exit mechanisms

Herpes Simplex Virus (HSV)

  • Types of HSV:
  • HSVI: Mainly causes cold sores
  • HSVII: Mainly causes genital herpes
Symptoms of Herpes Infections
  • Gingivostomatitis
  • Herpetic keratitis
  • Genital herpes
Viral Structure of HSV
  • Outside View: Contains envelopes and glycoproteins
  • Inside View: Viral nucleic acid and proteins

HSV Entry

  • Mechanism:
  • HSV uses glycoprotein gD for cell entry
  • gD binds to receptors on epithelial cells (e.g., HVEM, Nectin-1)
  • Fusion of the virion with the host cell membrane
Trafficking and Transcription
  • Once inside, viral capsid uses microtubules to reach the nucleus.
  • Viral DNA is released into the nucleus and undergoes transcription in three stages:
  1. Immediate-early
  2. Early
  3. Late

HSV Replication

  • Replication through rolling circle replication once it has produced initial copies.
  • Linear DNA is cut and packaged for progeny virion formation.
Exit from Host Cell
  • Assembly occurs at the inner nuclear membrane (INM)
  • Buds through INM, fuses with the outer membrane, and releases naked capsid into cytoplasm.
  • The modified virus exits via Golgi-mediated exocytosis.

HSV Latency

  • HSV can remain dormant in nerve cells and reactivation leads to cold sores or genital herpes.

Human Immunodeficiency Virus (HIV)

  • Member of the Retroviridae family.
  • Global Estimates (2023):
  • 39.9 million people living with HIV
  • 1.3 million new infections annually, with significant rates in Sub-Saharan Africa.
HIV Disease Mechanism
  • Infected Cells: CD4+ T cells, macrophages, dendritic cells.
  • Symptom progression spans from swollen lymph glands to systemic immune deficiency.

HIV Structure

  • Genome Components:
  • gag: Encodes structural proteins
  • pol: Encodes enzymes (reverse transcriptase, integrase)
  • env: Encodes envelope proteins (gp160)
  • Essential for interaction with host cell receptors (CD4 and CCR5).
Viral Life Cycle
  1. Entry: Virus binds to CD4 and co-receptors.
  2. Reverse Transcription: Utilizes reverse transcriptase to convert RNA to DNA.
  3. Integration: Viral DNA integrates into the host genome via integrase.
  4. Transcription and Translation: Produces mRNA for protein synthesis and viral genome replication.
  5. Budding: New virions are released from the host cell.
Antiretroviral Therapy (ART)
  • HAART: Highly Active Anti-Retroviral Therapy includes:
  • Entry inhibitors
  • Reverse transcriptase inhibitors (NRTIs and NNRTIs)
  • Protease inhibitors
  • Integrase inhibitors

Influenza Virus

  • Disease: Causes respiratory illness with fever, cough, fatigue, etc.
  • Impact: High prevalence (10%-20% of the population) and significant annual incidence (~36 million)
  • Historical Context: The 1918 pandemic resulted in approximately 20-40 million deaths.
Influenza Virus Structure
  • Composition: Segmented RNA genome (8 segments)
  • Contains genes for Hemagglutinin (HA), Neuraminidase (NA), Nucleoprotein, and others.
Mechanism of Action
  • Hemagglutinin: Binds to sialic acid on host cells for entry.
  • Neuraminidase: Essential for virus release from infected cells.
Antigenic Variability
  • Antigenic Drift: Gradual mutations during replication.
  • Antigenic Shift: Major changes due to reassortment of viral genomes.