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.