Human herpesvirus 8 variants (1998)

Published research on a new human herpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) grows increasingly confusing. Many studies of this virus are based on PCR, which can give false-positive contamination readings, even under the most stringent control conditions, as has happened in our own laboratory. PCR contamination, especially for nested PCR, is insidious because it can be intermittent or persistent. Sequencing of PCR products for polymorphisms, cannot reliably detect contamination because of the absence of Taq polymerase proofreading capacity. It was delightful to see this technique used to show that greater than 90% of sarcoidosis lesions (Luca Di Alberti and colleagues, Dec 6, p 1655)1Di Alberti L Piattelli A Artese L et al.Human herpesvirus 8 variants in sarcoid tissues..Lancet. 1997; 350: 1655-1661Summary Full Text Full Text PDF PubMed Scopus (157) Google Scholar are infected with HHV8/KSHV. This confirms a theory I have that there is not one virus detectable by PCR, but actually two. KSHV is rare in low-risk populations and is associated with Kaposi's sarcoma, body-cavity-based lymphomas, and a subset of Castleman's disease lesions by PCR, Southern-blot hybridisation, and serological testing. The epidemiology of this virus makes sense, and methods to find it, although far from perfect, are reliable and reproducible. HHV8, however, is totally different, and The Lancet has been in the forefront of publishing on the unusual epidemiology and biology of HHV8. It is a ubiquitous virus but is also responsible for a remarkable range of human diseases. For example, PCR detects HHV8 DNA in various posttransplant skin tumours of different origins,2Rady PL Yen A Rollefson JL et al.Herpesvirus-like DNA sequences in non-Kaposi's sarcoma skin lesions of transplant patients..Lancet. 1995; 345: 1339-1340Crossref PubMed Scopus (215) Google Scholar whereas KSHV is not present in these tumours.3Cathomas G Tamm M McGandy CE et al.Transplantation-associated malignancies: restriction of human herpes virus 8 to Kaposi's sarcoma.Transplantation. 1997; 64: 175-178Crossref PubMed Scopus (57) Google Scholar Published studies show that nested PCR can find HHV8 in over 90% of US HIV-positive semen donors,4Lin J-C Lin S-C Mar E-C et al.Is Kaposi's sarcoma-associated herpesvirus detectable in semen of HIV-infected homosexual men?.Lancet. 1995; 346: 1601-1602PubMed Scopus (105) Google Scholar whereas none of the 115 semen samples from low-risk healthy UK donors were positive for KSHV.5Howard MR Whitby D Bahadur G et al.Detection of human herpesvirus 8 DNA in semen from HIV-infected individuals but not healthy semen donors..AIDS. 1997; 11: F15-F19Crossref PubMed Scopus (94) Google Scholar Beyond its contribution to virology, the finding of HHV8 in sarcoid lesions1Di Alberti L Piattelli A Artese L et al.Human herpesvirus 8 variants in sarcoid tissues..Lancet. 1997; 350: 1655-1661Summary Full Text Full Text PDF PubMed Scopus (157) Google Scholar also could be of historical importance for providing the first carefully analysed phylogenetic dendrogram of Taq incorporation errors. In view of the frequency at which PCR water control samples are positive for HHV8, drinking water should be investigated as a source for transmission. On the basis of published results, HHV8/KSHV could cause skin tumours, sarcoidosis, multiple myeloma, encephalitis, prostate cancer, neurolymphomas, and other degenerative, autoimmune, neoplastic, and hyperplastic disorders. From haemorrhoids to hangovers, the search for HHV8 should proceed unimpeded by cautious trepidation or scientific consistency. In my experience, HHV8 can be detected reliably only by nested PCR, and one should avoid aerosol barrier-pipet tips or PCR machine bleaching to ensure the highest sensitivity. There is a danger here: intellectual fatigue will set in when readers of The Lancet find a new HHV8-related disease in each week's issue. As my colleague from medical school (Charles T Ellis, Homer, Alaska, USA) once prophetically told me: “If you were to take all the water buffalo in the world, and line them up. And then make them walk across a single point, all day long—it would be one helluva boring parade”. Alternatively, KSHV and HHV8 could be different names for the same virus. With cautious interpretation and use of appropriately reliable methods, we may yet find additional diseases caused by both viruses.