HUMAN FOAMY VIRUS PROTEINS ACCUMULATE IN NEURONS AND INDUCE MULTINUCLEATED GIANT-CELLS IN THE BRAIN OF TRANSGENIC MICE

Human foamy virus (HFV) is a retrovirus encoding structural genes and, like human immunodeficiency virus and human T cell leukemia virus I, several ancillary reading frames collectively termed the bel genes. We have previously shown that HFV transgenic mice develop an encephalopa thy with neuronal loss in hippocampus and cerebral cortex. We have now raised and characterized rabbit antisera to various recombinant porti ons of gag, pol, env, and bel-1, the viral transactivator. Immunoreact ivity for gag and bel-1 was observed in nuclei and processes of hippoc ampal and cortical neurons before the onset of morphological lesions a nd correlated with the appearance of HFV mRNA. Astrocyte-derived multi nucleated giant cells containing HFV proteins were present in the brai n of transgenic mice coexpressing full-length HFV genes but not in mic e expressing truncated gag and env, suggesting that these genes contai n a fusogenic domain. Expression of full-length structural genes decre ased the life expectancy of transgenic mice, implying an adjuvant role for these proteins in HFV-induced brain damage.