Human Herpesviruses (Chapters 41 and 42) Double-stranded DNA genome enveloped

1. Human Herpesviruses (Chapters 41 and 42) Double-stranded DNA genome enveloped Enquist et al., Principles of Virology, ASM, 2004 Genome = 125,000 - 236,000 base pairs

2. Herpesviridae family members share four significant biological properties: 1. Encode a large array of enzymes involved in a. nucleic acid metabolism (thymidine kinase, thymidylate synthetase, dUTPase, ribnucleotide reductase) b. DNA synthesis (DNA polymerase, helicase, primase) c. protein processing (protein kinases) 2. Synthesis of viral DNAs and capsid assembly occur in the nucleus, while final processing of virions occurs in the cytoplasm 3. Production of virus results in destruction of the infected cell 4. Able to exist in a latent state in their natural hosts while retaining the capacity to replicate and cause disease upon reactivation

3. Human Herpesviruses: (HHV-1) fever blisters Alpha herpesviruses (HHV-2) sexually transmitted genital lesions (HHV-3) chicken pox and shingles (HHV-5) Beta herpesviruses roseola (HHV-4) infectious mononucleosis Gamma herpesviruses

4. Transmission of Human Herpesviruses Most humans become infected with one or more herpesviruses Herpes viruses are fragile (enveloped) susceptible to heat, detergent, drying Generally require direct inoculation mucous membranes more susceptible than skin CMV and EBV can be transmitted through infected leukocytes VZV is mostly transmitted by aerosols

5. Herpesvirus Lytic cycle Cascade of gene expression Attach to and infect adjacent cells upon release Budding directly onto and into adjacent cells Therefore get a local spread of virus (predominantly) Syncytia can form

6. Virus replicates and assembles in the cell nucleus Get changes in nuclear structure - chromatin shifted to margins of nucleus Cowdry type A acidophilic intranuclear inclusion bodies Stained cells infected with a herpes virus show syncytia formation (multinucleated cells) and intranuclear inclusion bodies (darkly staining nuclear region).

7. Usual Course of Herpes Simplex Virus Infection and Disease 1. Acute disease facial or genital herpes, stomatitis, or keratitis localizied Exposure of skin, mucosa, or cornea to secretions containing virus Replication of virus in epithelial cells, causing vescular mucocutaneous lesions, stomatitis, or keratitis Spread to peripheral sensory or autonomic nerve endings and ganglia HSV-1 acquired very early in life (e.g. kissing) 2/3 of adults are Ab+ HSV-2 mostly transmitted by genital contact uncommon before adolescence 1/5 of adults are Ab+ Most HSV-1 and HSV-2 infections are asymptomatic ~1/3 of infections have recognizable symptoms

8. Usual Course of Herpes Simplex Virus Infection and Disease (continued) 2. Recovery Healing of lesions and establishment of latent infections in neurons 3. Latency Maintenance of latent infections in neurons

9. Usual Course of Herpes Simplex Virus Infection and Disease (continued) 4. Recurrent disease cold sores, fever blisters, keratitis, or genital lesions localizied Reactivation of latent virus and distal spread Recurrent lesions caused by virus replication in epithelial cells

10. Latent infections and reactivation (15.12)

11. Infections associated with Herpes Simplex Viruses Herpes keratitis - eye (can lead to scarring/blindness) Dendritic ulcer of cornea (Branching) (visualized with fluorescein) Wills Eye Institute, 2007 blindness after advanced herpes infection of the cornea Murray et al., Medical Microbiology, Elsevier, 2005

12. Herpetic stomatitis - most common viral infection of the mouth Primary infection by HSV-1 or HSV-2 vesicles on oral mucosa, the tongue, and gingivae confused with acute necrotizing ulcerative gingivitis (ANUG) when gingivae inflammed Herpes labialis (cold sore) reactivation of latent HSV-1 or HSV-2 Murray et al., Medical Microbiology, Elsevier, 2005 Primary herpes gingivostomatitis Herpetic dermatitis and herpetic whitlow (HSV-1 or HSV-2) Murray et al., Medical Microbiology, Elsevier, 2005 Herpetic whitlow