Relationship between beta‐herpesviruses reactivation and development of complications after autologous peripheral blood stem cell transplantation

Abstract

The relationship between beta-herpesviruses reactivation and the development of complications after autologous peripheral blood stem cell transplantation was investigated. Viral genomic sequences were detected by the polymerase chain reaction, virus-specific antibodies by ELISA, and human herpesvirus (HHV)-6 variants by restriction endonuclease analysis. Virus reactivation, serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, soluble IL-2 receptor (sIL-2R), IL-2, and IL-4 were compared with clinical features in 44 patients before and after transplantation. Anti-CMV and anti-HHV-6 antibodies were found in 70.5% and 81.8% of patients, respectively. The frequency of plasma viremia was significantly higher in patients after transplantation (41% vs. 11.4%). Reactivation of more than one virus was identified in 55.6% of patients and reactivation of HHV-7 alone in 44.4%. In cases of concurrent infection, HHV-7 was reactivated before HHV-6, and both HHV-6 and HHV-7 were reactivated before CMV. There was a significant increase in HHV-6 load in peripheral blood leukocytes DNA during viremia. In all cases HHV-6B variant was detected. Complications after transplantation occurred in 27.3% of patients and virus reactivation was detected in all patients with complications. The significant increases in the rate of HHV-6 and HHV-7 reactivation and in serum levels of TNF-α, IL-1β, and sIL-2R, as well as aggravated immunosuppression, suggest that both viruses were involved in the complications after autologous peripheral blood stem cell transplantation, via their immunomodulatory activity. The kinetics of reactivation suggests a potential role of HHV-7 as a co-factor of HHV-6 reactivation, and of both HHV-6 and HHV-7 as co-factors of CMV reactivation.

Inhibitors of Nucleotidyltransferase Superfamily Enzymes Suppress Herpes Simplex Virus Replication

“…Human pathogens include varicella-zoster virus (VZV) (73), which causes chicken pox and shingles; HCMV, which causes mental retardation and deafness in neonates and retinitis in immunocompromised patients (63); human herpesvirus 6 (HHV-6), which causes roseola infantum and febrile seizures (74); Epstein-Barr virus (EBV), which causes infectious mononucleosis and is associated with cancers, including Burkitt's lymphoma (75); HHV-7, which may stimulate HCMV reactivation and tissue transplant rejection (76); and HHV-8, which causes Kaposi's sarcoma (77). More than 90% of adults have been infected with and retain a latent form of one or more of these viruses.…”

Co-Infections with Cytomegalovirus and Human Herpesvirus Type 7 in Adult Polish Allogeneic Haematopoietic Stem Cell Transplant Recipients

“…Available data suggest that HHV-7 infections are common after transplantation and may lead to CMV reactivation and cytomegalovirus disease (Chan et al 1997; Chapenko et al 2012; Kidd et al 2000). In the present study, HHV-7 viraemia was found mostly (94 %) before CMV infection, which suggests a possible interaction between these β-herpesviruses.…”

“…On the other hand, the reactivation of HHV-7 virus is very rarely studied and its clinical significance remains still unknown (Ljungman et al 2008). Some authors have postulated a potential increase in virulence of HHV-7 in the course of a simultaneous CMV reactivation, leading to a greater risk of CMV disease after transplantation (Chan et al 1997; Chapenko et al 2012; Zawilińska et al 2011). …”

Classification of HHV-6A and HHV-6B as distinct viruses

“…HHV-6B is the dominant virus present in the peripheral blood mononuclear cells (PBMCs) of healthy adults, at least in industrialized countries, and is also the virus that reactivates in a significant majority of both solid organ and stem cell transplant cases in these countries [21, 28, 45, 53, 57, 65, 74, 100, 108, 128], while both HHV-6A and HHV-6B are detected with similar frequency in the plasma of bone marrow transplant patients [97, 114]. HHV-6B is also frequently detected in the GI tract of solid organ transplant patients [76], has been identified in endodontic abscesses [54], and is the virus found in adenoids and tonsils, particularly in children affected by upper airway infections [35].…”

“…In addition, although an overwhelming majority of post-transplant reactivation occurs with HHV-6B [28, 29, 53], HHV-6A DNA and mRNA are found more frequently than HHV-6B in patients with neuroinflammatory diseases such as multiple sclerosis (MS) [9, 14, 48, 115] and rhomboencephalitis [37]. HHV-6A has been found predominantly in the CNS of a subset of patients with MS, and active HHV-6A infection has been detected in blood [8, 9, 11] and in CSF [110] of patients with relapsing/remitting MS [8–10, 14, 20, 110, 115, 131].…”