Journal of Medical Virology 81:779–789 (2009) Predominant Human Herpesvirus 6 Variant A Infant Infections in an HIV-1 Endemic Region of Sub-Saharan Africa Matthew Bates, 1 Mwaka Monze, 2 Humphrey Bima, 2 Mirriam Kapambwe, 2 David Clark, 1 Francis C. Kasolo, 2,3 and Ursula A. Gompels 1 * 1 Pathogen Molecular Biology Unit, Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, University of London, London, United Kingdom 2 Virology Unit, University Teaching Hospital, Lusaka, Zambia 3 WHO Africa, Harare, Zimbabwe Human herpesvirus 6, HHV-6, commonly infects children, causing febrile illness and can cause more severe pathology, especially in an immune compromised setting. There are viru- lence distinctions between variants HHV-6A and B, with evidence for increased severity and neurotropism for HHV-6A. While HHV-6B is the predominant infant infection in USA, Europe and Japan, HHV-6A appears rare. Here HHV-6 prevalence, loads and variant genotypes, in asymptomatic compared to symptomatic infants were investigated from an African region with endemic HIV-1/AIDS. DNA was extracted from blood or sera from asymptomatic infants at 6 and 18 months age in a population-based micro- nutrient study, and from symptomatic infants hospitalised for febrile disease. DNA was screened by qualitative and quantitative real- time PCR, then genotyped by sequencing at variable loci, U46 (gN) and U47 (gO). HIV-1 serostatus of infants and mothers were also determined. HHV-6 DNA prevalence rose from 15% to 22% (80/371) by 18 months. At 6 months, infants born to HIV-1 positive mothers had lower HHV-6 prevalence (11%, 6/53), but higher HCMV prevalence (25%, 17/67). HHV-6 positive febrile hospitalized infants had higher HIV-1, 57% (4/7), compared to asymptomatic infants, 3% (2/74). HHV-6A was detected exclusively in 86% (48/56) of asymptomatic HHV-6 positive samples geno- typed. Co-infections with both strain variants were linked with higher viral loads and found in 13% (7/56) asymptomatic infants and 43% (3/7) HIV-1 positive febrile infants. Overall, the results show HHV-6A as the predominant variant sig- nificantly associated with viremic infant-infec- tions in this African population, distinct from other global cohorts, suggesting emergent infec- tions elsewhere. J. Med. Virol. 81:779–789, 2009. ß 2009 Wiley-Liss, Inc. KEY WORDS: HHV-6A; HHV-6B; herpesvirus recombination; emergent infections; exanthema subi- tum; multiple sclerosis; virus gene variation; HIV/AIDS INTRODUCTION Human herpesvirus 6 (HHV-6; family Herpesviridae, subfamily Betaherpesvirinae, genus Roseolovirus, species Human herpesvirus 6) has strain variants which have been grouped as variants A and B (HHV-6A and HHV-6B). There is variation within each grouping, but greater variation is observed between variant groups [Gompels and Kasolo, 2006]. Identification of variants serologically has not been possible routinely since the immunodominant antigens appear conserved and responses are cross-reactive. Grouping of primary infections has been done using samples of saliva or blood from children followed by PCR amplification of specific genes and DNA sequencing. Apart from studies of symptomatic or febrile children, it is difficult to discern the distribution of variants in the global population. Only two population-based surveys have been done, and these were in North America. These and related studies show that, while there is persistence in saliva, acute infection is followed by viraemia and detection of DNA in the sera, which is eventually cleared, and subsequent low levels or latent infection is detected in leukocytes. One study from the west coast *Correspondence to: Ursula A. Gompels, Pathogen Molecular Biology Unit, Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, University of London, London WC1E 7HT, UK. E-mail: ursula.gompels@lshtm.ac.uk Accepted 14 January 2009 DOI 10.1002/jmv.21455 Published online in Wiley InterScience (www.interscience.wiley.com) ß 2009 WILEY-LISS, INC.