Approximately 8% of the genomes of mammals, including humans and mice, are comprised of retroviral elements acquired by infection of germ line cells during the course of evolution. Retroviral insertions in our genome number about 40,000 and are in the same range as the total number of genes encoded by our DNA. Most endogenous retrovirus elements are defective for replication however several contain one or more viral genes that are expressed during development and certain physiological or pathological conditions. Little is known about the control of retrovirus expression or the influence of such expression on the physiology or pathology of the host. An extensively investigated group of endogenous retroviruses are those giving rise to recombinant murine leukemia viruses (MuLVs) in mice. Upon infection of mice with exogenous ecotropic MuLVs, members of this group undergo recombination to generate new MuLVs with an altered infectious host range. Recombination requires transcription of the endogenous retroviruses. Although the endogenous polytropic proviruses are transcribed;replication of the endogenous polytropic viruses in the absence of recombination has not been observed. This may, in many cases, reflect defects such as point mutations or deletions in the endogenous viral genome but may also be influenced by the activity of various restriction factors. The fact that exogenous MuLVs are capable of replicating in mice indicates that they have evolved mechanisms to circumvent the activity of at least some of the restriction factors such as the murine APOBEC3. Thus, exogenous retroviruses might facilitate through complementation, active replication of endogenous retroviruses. We have found that infection of mice by an exogenous virus results in the infectious transfer of complete endogenous proviral genetic sequences. This includes proviruses which are severely defective and possess large deletions as well as proviruses that are full-length. Furthermore, the transferred sequences are transcribed and packaged into virions released from the newly infected cells. At early times after infection with the Friend MuLV, packaging and transfer of intact endogenous retroviruses is much more prevalent than recombination. We have extended these studies to find that that transfer of endogenous retroviruses can be observed as early as one day after infection indicating that packaging occurs after a single replication cycle in the initially infected cells. Further, transfer occurs from C57/Bl6 mice from which the prototypic mouse genomic sequence was derived. This finding will greatly facilitate the characterization of the packaged endogenous transcripts. C57/Bl6 mice do not generate recombinant polytropic MuLVs thus our observations indicate that this block is not due to packaging or transcription of the endogenous virus. The mobilization of intact endogenous retroviruses is unprecedented and may have important implications for the involvement of endogenous retroviruses in disease processes. The endogenous retroviral envelope glycoprotein, gp70 is implicated in murine lupus nephritis. This protein is secreted by hepatocytes as an acute phase protein and has been believed to be a product of an endogenous xenotropic virus. However, since endogenous polytropic viruses encode gp70s that are closely related to xenotropic gp70, these viruses could be additional sources of serum gp70. To better understand the genetic basis of the expression of serum gp70, we analyzed the abundance of xenotropic and polytropic gp70 RNAs in livers and the genomic composition of corresponding endogenous proviruses in various strains of mice, including two different Sgp (serum gp70 production) congenic mice (Sgp3 and Sgp4). These studies revealed a significant contribution of polytropic gp70s to serum gp70. We have now exended these studies to show that expression levels of a subclass of polytropic MuLVs, termed, modified polytropic (mPT), are highly elevated in mice which develop systemic lupus erythematosus. This elevated expression appears specific for this class of endogenous viruses and under the control of the Sgp3 locus. Interestingly, only the full-length env transcripts are elevated while env genes encoding defective deleted env transcripts are not. .