Human Herpesvirus-8

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Human Herpesvirus-8

• Krystle Jones

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Background

• HHV-8 was discovered in 1994 by Yuan Chang and
  his collaborators at Columbia University.
• Polymerase Chain Reaction (PCR) technique allowed
  them to isolate 2 fragments of DNA in tissues
  infected with both AIDS and Kaposis Sarcoma.
• First known human member of the genus
  Rhadinovirus.
• Also known as Kaposis Sarcoma-Associated
  Herpesvirus.

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What is a Herpesvirus?

• A group of double-stranded DNA viruses that are
  enveloped and have large, complex genomes.
• Belong to family Herpesviridae, which is divided
  into 3 sub-families Alphaherpesvirinae,
  Betaherpesvirinae, and Gammaherpesvirinae.
• Herpesviruses are made up of a core, capsid,
  tegument, and envelope.

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• Different herpesviruses vary in genomic sequences
  and proteins, but are highly conservative in
  terms of structure and organization.
• Success of these infections depends on 3
  strategies
• 1-The capability of the virus to enter the host
  cell quickly and efficiently, and begin
  replication and production immediately.
• 2-Ability to avoid attacks from host by
  inhibiting splicing of mRNA, which blocks the
  presentation of antigenic peptides on the cell
  surface.
• 3-Ability to hide their genome and remain at a
  latent phase of infection until a phase of
  immunosuppression occurs.

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HHV-8 Genomes

• -All herpesvirus genomes have 2 regions bound by
  inverted repeats.
• -The 2 separated regions are the unique long and
  unique short regions.
• -These allow for rearrangements so that the
  genomes can then exist as a mixture of 4 isomers.

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HHV-8

• Is an opportunistic pathogen- after the primary
  infection, HHV-8 hides in the body until a period
  of low immunity.
• HIV patients tend to be infected by
  microorganisms such as HHV-8 because of the loss
  of their CD4 T-cells, and reactivation occurs
  when the latent virus is no longer controlled by
  CD8 T-cells.

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• -HHV-8 has a capsid composed of 4 structural
  proteins. 3 are encoded by ORF 25, 26, and 62.
• -Some proteins found in HHV-8 that are similar to
  those found in cellular proteins are
• -complement binding protein
• -IL6-like cytokine
• -3 chemokines
• -Interferon regulatory factor
• -cell-adhesion-like molecules
• -G-protein coupled receptor
• -HHV-8 has been found in B-cells, macrophages,
  and dendritic cells.

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HHV-8 Global Infection
HHV-8 is transmitted sexually through semen, and
sometimes vertically from mother to child.
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Kaposis Sarcoma

• Is a tumor that generally appears in the tissues
  below the skin surface of the face and genitalia.
• Is closely associated with HHV-8.
• There are 4 different forms of KS
• AIDS-related
• Classic
• Acquired
• African

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The formation of KS lesions in association with
the infection of HHV-8 is commonly seen, and is
the source of DNA in HHV-8 research.
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Detection and Treatment

• Detection of HHV-8 depends on direct
  identification of the viral DNA. This can be done
  through blood screening or with the tissue of KS
  lesions.
• Neither KS nor HHV-8 are curable at this point.
• Most effective way to suppress both KS and HHV-8
  is to treat the symptoms of HIV.
• Antibody tests
• ELISA
• Immunofluorescent Assay (IFA)

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Current Research

• In recent studies of lymphoma cancers, a viral
  protein called vFLIP K13 has been found to mimic
  the signaling functions of caspase 8, leading to
  the proliferation of lymphocytes.
• The protein activates a cellular pathway called
  NF-?B that is involved in the development of
  lymphoma.
• The NF-?B pathway may be a good target for
  therapies directed at HHV8-associated tumors.

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References

• Detailed Guide What is Kaposis Sarcoma?
  (2005). Medline Plus and American Cancer Society,
  USA. http//www.cancer.org/docroot/cri/content/cr
  i_2_4_1x_what_is_kaposis_sarcoma_21.asp?sitearea
• Herpesvirus Family Herpesviridae. (2005).
  University of Chicago, Chicago, Illinois.
  lthttp//www.stdgen.lanl.gov/stgen/bacteria/hhv8/he
  rpes.htmlgt.
• Herpesviruses HHV-8. (2005). University of
  Leicester, Leicester, England. lthttp//www-micro.m
  sb.le.ac.uk/3035/HHV8.htmlgt.
• "The AIDS Knowledge Base Section 7.2 - Human
  Herpesvirus 8 and AIDS-Related Neoplasms."
  (2001). University of California, San Francisco,
  CA 94143, USA. lthttp//hivinsite.ucsf.edu/InSite.j
  sp?pagekb-06dockb-06-02-01gt.
• Richman, D. et. al. (1997). Clinical Virology.
  New York Churchill Livingstone.
• Paoli, Paolo. Human herpesvirus 8 an
  update. Microbes and Infection 6.3 (2004)
  328-335.