An animal model for human EBV-associated hemophagocytic syndrome: herpesvirus papio frequently induces fatal lymphoproliferative disorders with hemophagocytic syndrome in rabbits.
Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis. However, the animal model for EBV-AHS has not been developed. We reported the first animal model for EBV-AHS using rabbits infected with EBV-related herpesvirus of baboon (HVP). Eleven of 13 (85%) rabbits inoculated intravenously with HVP-producing cells developed fatal lymphoproliferative disorders (LPD) between 22 and 105 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in nine of these 11 rabbits. The peroral spray of cell-free HVP induced the virus infection with increased anti-EBV-viral capsid antigen-IgG titers in three of five rabbits, and two of these three infected rabbits died of LPD with HPS. Autopsy revealed hepatosplenomegaly and swollen lymph nodes. Atypical lymphoid T cells expressing EBV-encoded small RNA-1 infiltrated diffusely in many organs, frequently involving the lymph nodes, spleen, and liver. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by polymerase chain reaction or Southern blot analysis. Reverse transcriptase-polymerase chain reaction revealed both HVP-EBNA1 and HVP-EBNA2 transcripts, suggesting latency type III infection. These data indicate that the high rate of rabbit LPD with HPS induction is caused by HVP. This system is useful for studying the pathogenesis, prevention, and treatment of human EBV-AHS.
Hayashi
K
K
Second Department of Pathology, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama-city 700-8558, Japan. kazuhaya@med.okayama-u.ac.jp
Ohara
N
N
Teramoto
N
N
Onoda
S
S
Chen
H L
HL
Oka
T
T
Kondo
E
E
Yoshino
T
T
Takahashi
K
K
Yates
J
J
Akagi
T
T
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D002460:Cell Line; D004195:Disease Models, Animal; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D016679:Genome, Viral; D006566:Herpesviridae Infections / Q000150:complications*; D006568:Herpesvirus 1, Cercopithecine; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D015616:Histiocytosis, Non-Langerhans-Cell / Q000821:virology*; D006801:Humans; D016130:Immunophenotyping; D008232:Lymphoproliferative Disorders / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000821:virology*; D010215:Papio; D011817:Rabbits
D000914:Antibodies, Viral