Human Herpesvirus (HHV)–6 and HHV–7: Two Closely Related Viruses with Different Infection Profiles in Stem Cell Transplantation Recipients

Abstract

Human herpesvirus (HHV)-6 and HHV-7 loads were evaluated retrospectively in peripheral blood mononuclear cells (PBMC) from 78 recipients of stem cell transplantation (SCT) by real-time polymerase chain reaction. The median HHV-6 load in patients was 1357 genome equivalent copies (EqCop)/10(6) PBMC but was below the quantitation threshold in 31 immunocompetent individuals, which strongly suggests that HHV-6 reactivation occurred after SCT. The HHV-6 load was higher in patients with delayed neutrophil engraftment (P=.002) or severe graft-versus-host disease (P=.009). Moreover, the occurrence of at least 1 HHV-6-related manifestation (fever, cutaneous rash, pneumonitis, or partial myelosuppression) was statistically associated with a concomitant virus load >10(3) EqCop/10(6) PBMC (P=.007). Conversely, HHV-7 reactivation was not favored, because median HHV-7 loads were similar in patients and healthy control subjects (1053 vs. 1216 EqCop/10(6) PBMC). The kinetics of Roseolovirus loads during the posttransplantation period suggested that HHV-7 may act as a cofactor of HHV-6 reactivation.

Effect of HHV-6 and HHV-7 Infection on the Posttransplant Process and the Development of Complications in Patients after Autologous Stem Cell Transplantation / HHV-6 Un HHV-7 Infekcijas Ietekme Uz Pēctransplantācijas Klīnisko Gaitu Un Komplikāciju Attīstību Pacientiem Pēc Autologas Cilmes Šūnu Transplantācijas

“…The reactivation of HHV-7 is observed before HHV-6 reactivation, which may suggest potential interaction between these viruses. These results are in accordance with those obtained in previous studies conducted in vitro (Katsafanas et al, 1996) and in vivo (Maeda et al, 2000;Boutolleau et al, 2003;Hall et al, 2006). However, Sassenscheidt et al (2006), Humar et al (2009), Tormo et al (2010 did not find evidence for potential interaction between HHV-6, HHV-7, and CMV.…”

“…The ubiquitous nature of beta-herpesviruses creates conditions for the development of concurrent infection and interaction between these viruses. The kinetics of the activation of these viruses during the post-transplantation period suggests that HHV-7 can act as a co-factor for HHV-6 and CMV reactivation, while both -HHV-6 and HHV-7 can act as co-factors in CMV disease development (Miyoshi et al, 2001;Boutolleau et al, 2003). The prevalence of human herpesvirus reactivation ranges from 40 to 60% in auto-HSCT patients and usually occurs within 2-4 weeks (Zerr et al, 2005).…”

Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source

“…22 Thus, we postulate that HHV6 originates from the reactivation of endogenous HHV6. Compared with MUD, in which the results were in the range of most reported studies, 22,24,25 CBT showed a significant by higher incidence and an higher median viral load of HHV6 infections and for a longer period of time after transplant. It was described earlier in three studies but with a short follow-up post transplant.…”

“…In our study, along with others, we have already reported the main consequence of HHV6 infection was to delay neutrophil and plt recoveries, especially in early reactivating patients. 25,27,37 Delayed engraftment is a well-known complication of cord blood transplant occurring at a higher incidence when compared with other source of SCs. [1][2][3][4]6 The role of HHV6 in delayed engraftment raises logically the question of HHV6 prophylaxis in CB transplant.…”

Long-Lasting CD3 + T-Cell Deficiency after Cord Blood Stem Cell Transplantation in a Human Herpesvirus 6-Infected Child

“…The length of the active infection (about 8 months) is the longest reported so far (1,5,8). Moreover, the viral load was constantly over 10 3 copies/10 5 PBMCs, which is regarded as the threshold value for an active viral replication and is considered a good marker for the onset of or association with relevant clinical disorders (1).…”