HHV-6B-induced neutropenia in primary infection associated with specific chemokines

In an article published in the Pediatric Infectious Disease Journal, Tetsushi Yoshikawa’s team from Fujita Health University School of Medicine determined that the severe neutropenia in primary HHV-6B infection is tied to reduced platelet counts, lower RANTES and higher levels of MCP-1, MIG and IP-10. These chemokines are known to be strong chemoattractants for activated T cells and monocytes/macrophages, and RANTES is a potent chemoattractant for neutrophils.

HHV-6 reactivation has long been known to cause bone marrow suppression in transplant patients, and several studies have suggested that reactivation delays platelet recovery, a phenomenon often observed in hematopoietic stem cell transplant patients (Hashimoto 2002, Radonic 2005). This thrombocytopenia is thought to be a complication of HHV-6B-induced exanthem subitum, and previous authors have suggested that this results from direct virus-associated bone marrow suppression rather than from immune-mediated mechanisms in the peripheral circulation (as seen in acute idiopathic thrombocytopenic purpura or disseminated intravascular coagulation) (Hashimoto 2002)

Dr. Yoshikawa’s detailed study of patients with severe neutropenia is the first of its kind, evaluating fifty-four patients with primary HHV-6B infection, with serial blood sampling conducted 1-4 days before and 5-10 days after the onset of illness. Severe neutropenia was defined as a neutrophil count less than 500 cells/µL, and patient characteristics, clinical data, and cytokines and chemokines levels were compared between the patients with (16) and without (38) neutropenia. While cytokine levels were found to be similar between the two groups, AST levels were significantly elevated in the group with neutropenia

Importantly, the authors also point out that HHV-6 U12 and U51 encode a functional chemokine receptor that can bind to RANTES directly or down-regulate RANTES expression, resulting in immune evasion (Milne 2000, Isegawa 1998). Therefore, the authors believe it possible that the syntheses of U12 and U51 were preferentially up-regulated secondary to HHV-6B infection in the patients with severe neutropenia. The authors observed that the course HHV-6B-associated neutropenia was largely transient in their cohort, but propose that further study should be done to determine if HHV-6B might cause prolonged neutropenia as is the case with closely related CMV (Vlacha 2007).

For more information, read the full paper.