First data on the molecular genetic diversity of HHV6B and its impact on the clinical and laboratory course of mononucleosis-like syndrome in children

Human herpes virus 6B (HHV6B) is a ubiquitous causative agent of mononucleosis-like syndrome (MLS) and other diseases. The diversity of HHV6B infection may be due to virus genetic polymorphism. Molecular genetic diversity of circulating HHV6B, as well as its impact on the clinical and laboratory features of HHV6B infection have not been studied. The aim of the work was to study the intraspecific diversity of HHV6B circulating among children in Nizhny Novgorod (Russia) region, and to investigate its effect on MLS clinical and laboratory features. Blood leukocytes and saliva DNA samples from healthy children and children with HHV6B infection were analyzed for HHV6B DNA detection. Original intraspecific HHV6B classification based on detecting signature nucleotide substitutions in the sequence of the U90 gene fragment, was used for virus typing. A relationship between HHV6B genovariant and clinical/laboratory MLS characteristics was studied using multivariate statistical methods. Circulation of four HHV6B genovariants was shown among children in Nizhny Novgorod region: HHV6B/GV2e, HHV6B/GV2b (dominant genovariants), HHV6B/GV1a and HHV6B/GV2a (minor genovariants). Children with MLS infected with HHV6B/GV2e genovariant were more likely to have laboratory signs of cytolysis and increased peripheral blood lymphocyte count. Children with MLS infected with the HHV6B/GV2b genovariant were more likely to have higher mature neutrophil level. An increase of HHV6B viral load in leukocytes was accompanied by aggravated intoxication symptoms. Co-infection with the Epstein–Barr virus (EBV) led to more severe symptoms of acute tonsillitis, hepatosplenomegaly, and lymphadenopathy. Patients with EBV were more likely to have higher ALAT and lymphocyte level along with decreased mature neutrophil count. In children with MLS, EBV coinfection caused smaller HHV6B viral load in blood leukocytes (in children with HHV6B DNA 10 or more copies/105 cells) and lower HHV6B DNA detection frequency in saliva (in children with HHV6B DNA less than 10 copies/105 leukocytes). The results show the influence of genetic HHV6B polymorphism upon the clinical and laboratory features of MLS in children, and also demonstrate that HHV6B/GV2e and EBV cause similar disease symptoms.