Cardiac pathology and molecular epidemiology by avian leukosis viruses in Japan.
Epidemiological studies suggest that retroviruses, including human immunodeficiency virus type 1, are associated with cardiomyopathy and myocarditis, but a causal relationship remains to be established. We encountered unusual cardiomyocyte hypertrophy and mitosis in Japanese native fowls infected with subgroup A of the avian leukosis viruses (ALVs-A), which belong to the genus Alpharetrovirus of the family Retroviridae and mainly induce lymphoid neoplasm in chickens. The affected hearts were evaluated by histopathology and immunohistochemistry, viral isolation, viral genome sequencing and experimental infection. There was non-suppurative myocarditis in eighteen fowls and seven of them had abnormal cardiomyocytes, which were distributed predominantly in the left ventricular wall and showed hypertrophic cytoplasm and atypical large nuclei. Nuclear chains and mitosis were frequently noted in these cardiomyocytes and immunohistochemistry for proliferating cell nuclear antigen supported the enhancement of mitotic activity. ALVs were isolated from all affected cases and phylogenic analysis of envSU genes showed that the isolates were mainly classified into two different clusters, suggesting viral genome diversity. In ovo experimental infection with two of the isolates was demonstrated to cause myocarditis and cardiomyocyte hypertrophy similar to those in the naturally occurring lesions and cardiac hamartoma (rhabdomyoma) in a shorter period of time (at 70 days of age) than expected. These results indicate that ALVs cause myocarditis as well as cardiomyocyte abnormality in chickens, implying a pathogenetic mechanism different from insertional mutagenesis and the existence of retrovirus-induced heart disorder.
Laboratory of Comparative Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Sayuri
S
Nakamura
Laboratory of Comparative Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Kenji
K
Ochiai
Miho Training Center, Japan Racing Association, Utsunomiya, Japan.
Akihiro
A
Ochi
Medical School, Okayama University, Okayama, Japan.
Hiroki
H
Yabushita
Kenpoku Meat Hygiene Inspection Institute, Tochigi Prefecture, Ohtawara, Japan.
Asumi
A
Abe
Laboratory of Comparative Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Sayaka
S
Kishi
Laboratory of Comparative Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Yuji
Y
Sunden
Laboratory of Comparative Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Takashi
T
Umemura
D000818:Animals; D001353:Avian Leukosis / Q000150:complications / Q000473:pathology / Q000821:virology*; D001354:Avian Leukosis Virus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D006332:Cardiomegaly / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D002645:Chickens / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D016679:Genome, Viral; D006801:Humans; D007124:Immunoenzyme Techniques; D017720:Molecular Epidemiology; D009205:Myocarditis / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011201:Poultry Diseases / Q000453:epidemiology* / Q000209:etiology; D012207:Rhabdomyoma / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D014779:Virus Replication
D004279:DNA, Viral