Medical Microbiology Herpesvirus I and II Fall, 2009 INSTRUCTOR: Dr. J. David Gangemi OBJECTIVE: Introduction to virus biology, pathogenesis, disease characteristics, prevention and treatment REFERENCE: Murray, 6th Edition, Chapter 54
INSTRUCTOR: Dr. J. David Gangemi
OBJECTIVE:Introduction to virus biology, pathogenesis, disease characteristics, prevention and treatment
REFERENCE:Murray, 6th Edition, Chapter 54
III. Immune Response to Infection
IV. Neurovirulence and latency
V. Treatment and Control
“Herpes”…..to creep or crawl. Term used to describe the spreading nature of skin lesions.
From Queen Mab, the midwife of the fairies….
“O’er ladies lips, who straight on kisses dream, which oft the angry Mab with blisters plagues, because their breaths with sweetmeats tainted are”
25 viruses in the family Herpetoviridae-
a number of these are known to infect man:
In recovery from herpetic infections, the cellular arm of the immune response appears to have the greater role (agammaglobulinemics recover from infection if they have normal T cell functions)
Interferon, cytotoxic T-lymphocytes, NK cells and macrophages in acute and in recurrent infections
Herpes simplex and varicella zoster viruses have two unique biologic properties that influence human disease……. the capacity to invade and replicate in the CNS and the capacity to establish a latent infection.
Dynamic state-- persistence of low levels of infectious virus in sensory ganglia, neurons may or may not killed retrograde vs anterograde transport of virus through peripheral sensory nerve endings
Static state -- DNA of virus is maintained in a non-replicating state at some extrachromosomal site in neuron or is integrated into cellular DNA
HSV and VZV….acycloguanosine (acyclovir) and prodrugs valacyclovir and famciclovir (famciclovir is prodrug of penciclovir)
CMV…ganciclovir; phosphonoacetate, interferon
Agents that inactivate: ethyl ether, chloroform, glutaraldehyde; phototherapy with neutral red
Immunologic approaches: vaccination with live attenuated virus for chickenpox (varicella-zoster); experimental live virus and HSV subunit vaccines (in development)
Primary infection with HSV-1 or HSV-2 virus may result in latency--that is, the virus goes into a dormant existence in which no clinical features are apparent. However, with an appropriate stimulus such as sunlight, fever, menstration, or emotional stress, the virus may reactivate and produce disease sequelae.
Note-Both primary infections with HSV and endogenous recurrences may be asymptomatic and produce immune responses without overt clinical signs and symptoms
Cold sores (labialis)
Genital lesions (herpes genitalis)
1. Varicella(chickenpox): Usually mild disease (except in immunosuppressed) with characteristic rash and pox formation. Begins as respiratory infection then disseminates.
2. Herpes Zoster (shingles): Reactivation of latent varicella virus…..cause of reactivation unknown.
3.Cytomegaloviruses(CMV): A ubiquitous virus shed persistently by infected hosts...disease in those with abnormal CMI. Is responsible for a form of mononucleosis which is heterophile negative.
4. Epstein-Barr virus (EBV): Etiologic agent of infectious mononucleosis which is heterophile positive.
*Other members of the Shingles Prevention Study Group are listed in the Appendix
Ann Arvin, M.D. NEJM June 2, 2005: Vol 352 NO. 22