Spontaneous fusion of cells between species yields transdifferentiation and retroviral transfer in vivo.
Human cells can fuse with damaged or diseased somatic cells in vivo. Whether human cells fuse in vivo in the absence of disease and with cells of disparate species is unknown. Such a question is of current interest because blood exchanges between species through direct physical contact, via insect vectors or parasitism, are thought to underlie the transmission of zoonotic agents. In a model of human-pig chimerism, we show that some human hematopoietic stem cells engrafted in pigs contain both human and porcine chromosomal DNA. These hybrid cells divide, express human and porcine proteins, and contribute to porcine nonhematopoietic tissues. In addition, the hybrid cells contain porcine endogenous retroviral DNA sequences and are able to transmit this virus to uninfected human cells in vitro. Thus, spontaneous fusion can occur in vivo between the cells of disparate species and in the absence of disease. The ability of these cell hybrids to acquire and transmit retroviral elements together with their ability to integrate into tissues could explain genetic recombination and generation of novel pathogens. * differentiation * fusion * retrovirus
Ogle
Brenda M
BM
Transplantation Biology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Butters
Kim A
KA
Plummer
Timothy B
TB
Ring
Kevin R
KR
Knudsen
Bruce E
BE
Litzow
Mark R
MR
Cascalho
Marilia
M
Platt
Jeffrey L
JL
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000821:virology; D001805:Blood Transfusion, Intrauterine; D002454:Cell Differentiation; D002459:Cell Fusion; D002460:Cell Line; D002461:Cell Line, Transformed / Q000821:virology; D019070:Cell Lineage; D002871:Chromosome Banding; D004279:DNA, Viral / Q000032:analysis; D020077:Endogenous Retroviruses / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification*; D005347:Fibroblasts / Q000166:cytology / Q000821:virology; D015751:Genes, pol; D005819:Genetic Markers; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D006822:Hybrid Cells / Q000821:virology*; D007668:Kidney / Q000166:cytology; D009928:Organ Specificity; D011003:Ploidies; D012192:Retroviridae Infections / Q000635:transmission*; D012867:Skin / Q000166:cytology; D013045:Species Specificity; D013552:Swine / Q000033:anatomy & histology* / Q000821:virology; D018183:Transplantation Chimera / Q000097:blood / Q000821:virology; D014183:Transplantation, Heterologous
D004279:DNA, Viral; D005819:Genetic Markers