Human Herpesvirus-8
Krystle Jones
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 Kaposi’s Sarcoma.
• First known human member of the genus Rhadinovirus.
• Also known as Kaposi’s Sarcoma-Associated Herpesvirus.
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 subfamilies: Alphaherpesvirinae, Betaherpesvirinae, and
Gammaherpesvirinae.
• Herpesviruses are made up of a core, capsid, tegument, and
envelope.
• 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.
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.
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.
-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.
HHV-8 Global Infection
HHV-8 is transmitted sexually through semen, and sometimes vertically from
mother to child.
Kaposi’s 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
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.
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 HHV8 is to treat the symptoms of HIV.
• Antibody tests:
– ELISA
– Immunofluorescent Assay (IFA)
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-ĸB that is involved in the development of
lymphoma.
• The NF-ĸB pathway may be a good target for
therapies directed at HHV8-associated tumors.
References
“Detailed Guide: What is Kaposi’s Sarcoma?” (2005). Medline Plus and American Cancer Society, USA.
http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_is_kaposis_sarcoma_21.asp?sitearea
“Herpesvirus Family: Herpesviridae.” (2005). University of Chicago, Chicago, Illinois.
<http://www.stdgen.lanl.gov/stgen/bacteria/hhv8/herpes.html>.
“Herpesviruses: HHV-8.” (2005). University of Leicester, Leicester, England. <http://wwwmicro.msb.le.ac.uk/3035/HHV8.html>.
"The AIDS Knowledge Base: Section 7.2 - Human Herpesvirus 8 and AIDS-Related Neoplasms." (2001).
University of California, San Francisco, CA 94143, USA.
<http://hivinsite.ucsf.edu/InSite.jsp?page=kb-06&doc=kb-06-02-01>.
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.