Human herpes Virus

Pardon Papa has He Has POX

• this is a mnemonic to remember which viruses are enveloped DNA viruses, which are herpes, hepdna & POX

  

human Herpes virus family

• all human herpes have a Lrg genome, linear double stranded DNA & enveloped viruses

• HSV1, HSV2, painful vesicles on face & genitals, respectively

• VZV, varicella (chicken pox) & zoster (shingles) when it recurs

• EBV, infectious mononucleosis

• CMV, congenital infections, immunocompetent adults: asymptomatic infections, mononucleosis

• HHV6/7, roseola

• HHV8, Kaposi sarcoma(KSHV)

• hallmark of HSV is latent infection

Herpes Family Structure

• Linear, dsDNA

  • linear dbl stranded DNA

• Icosahedral capsid

  • symmetrical, 20-sided (icosahedral) protein shell that encloses the genetic material of certain viruses.

  • shape is highly efficient for enclosing viral genomes using a minimal number of protein subunits, providing both structural stability & ease of assembly.

• Tegument “matrix”

  • viral “matrix” – space btwn nucleocapsid & envelope, contains proteins & enzymes for viral DNA replication after infection

• Enveloped

herpes family replication

• Entry of viral DNA results in :

  • Active infection targets one cell type. Lysis of infected cells & CMI to infected cells are responsible for symptoms.

  • Latent infection targets another cell type & is associated w asymptomatic carriage.

• Note that virion assembly occurs in NUCLEUS, ER, GOLGI

• Virus is released by exocytosis OR cell lysis

• Cell-cell release enables infections w/o virus exposure to extracellular environment – EVASION OF IMMUNE SYSTEM

  steps of herpes replication simplified

• attachment, penetration, uncoating, synthesis, assembly, release

• The virus binds to specific receptors & fuses w the plasma membrane.

• The nucleocapsid then delivers the DNA genome to the nucleus.

• Transcription & translation occur in three phases: immediate early, early, & late.

• Immediate early proteins promote the takeover of the cell; early proteins consist of enzymes, including the DNA-dependent DNA polymerase; & the late proteins are structural & other proteins, including the viral capsid & glycoproteins.

• The genome is replicated before transcription of the late genes.

• Capsid proteins migrate into the nucleus, assemble into icosadeltahedral capsids, and are filled w the DNA genome.

• The capsids filled w genomes bud through the nuclear & endoplasmic reticulum (ER) membranes into the cytoplasm, acquire tegument proteins, & then acquire their envelope as they bud through the viral glycoprotein-modified membranes of the trans-Golgi network.

• The virus is released by exocytosis or cell lysis.

  herpes family properties

• Each have a common name and an HHV# designation (HHV=human herpes virus) & are divided by Host cell targets

• HHV genome encodes viral DNA polymerase*

• Replication in nucleus

• Virus packaging in nucleus, ER, and Golgi apparatus

• virus release through exocytosis or lysis

• Establish lytic, persistent, and latent infections

• Some HHV are associated with cancer development (EBV, KSHV)

• *Viral polymerases are frequently drug-able targets

herpes is ubiquitous everywhere all the time

• HSV1/2: “Mixing and matching of mucous membranes” or via direct contact of infected fluid from vesicles

• VSV: Aerosol or direct contact of infected fluid from vesicles

• CMV: Aerosol (saliva), sexual, vertical or parental transmission

• EBV: Saliva “Kissing disease”

• HHV6/7/8: Unknown