Nucleotide sequence of the intracisternal A-particle genome inserted 5'' to the interleukin-3 gene of the leukemia cell line WEHI-3B.

The nucleotide sequence of the intracisternal A-particle genome IAP-IL3 is presented. This IAP element was found to have inserted upstream of the promoter of the interleukin-3 gene of the leukemia cell line WEHI-3B. IAP-IL3 is 5095 bp in length, with identical long terminal repeats (LTRs) of 337 bp. The LTRs show many of the conserved sequence elements identified in other retroviruses. Comparison with other available sequences of IAP genomes indicates that IAP-IL3 is a deleted type I element. It carries a deletion covering the 3' end of the putative IAP gag gene and extending into the 5' end of the putative IAP pol gene. IAP-IL3 has extensive sequence homology with an IgE-binding factor cDNA and evidence is presented indicating that it was derived from a member of the mouse IAP sequence family. Comparison between the pol region of IAP-IL3 and other retroviruses suggests that IAP-IL3 is most closely related to type B and type D retroviruses.     

Identification of a novel family of human endogenous retroviruses and characterization of one family member, HERV-K(C4), located in the complement C4 gene cluster.

We have identified a novel family of about 10-50 human endogenous retrovirus elements (HERVs) and have characterized one family member (HERV-KC4). This retrovirus element is integrated within intron 9 of and complement C4A genes and also in some C4B genes, and is a principal contribution to interlocus and interallelic length heterogeneity of C4 genes. The HERV-K(C4) sequence has a typical retrovirus structure with elements of gag, pol and env domains, flanked by two long terminal repeats (LTRs) and is similar to type A, B and D retroviruses. Multiple termination codons preclude the existence of long open reading frames, suggesting that the HERV-K(C4) sequence is no longer functional. Zoo blot hybridization reveals that New World monkeys appear to lack sequences similar to HERV-K(C4), suggesting that integration has occurred after the divergence of Old and New World monkeys. Retrotransposition of prototype viruses is presumed to have led to the amplification and integration of the members of the family in different loci, which in humans, appear to be dispersed over several chromosomes. The absence of the HERV-K(C4) element in some C4B genes in both humans and orangutangs indicate that the retrovirus inserted into the C4A gene after the duplication of the cluster. Subsequent spread of the HERV-K(C4) sequence to C4B genes presumably occurred by interlocus sequence exchange mechanisms, such as unequal crossover and gene conversion-like mechanisms.     

Apparent recombinants between virus-liKE (VL30) and murine leukemia virus-related sequences in mouse DNA.

VL30 elements are a dispersed multigene family that is ubiquitous in all murine cells. Despite not sharing nucleic acid sequence homology with natural retroviruses (exogenous or endogenous), VL30 elements are distinguished by several retrovirus-like features. By screening a mouse embryonic library, we have cloned DNA units that contain VL30 sequences linked to MuLV-related sequences. Using blot hybridization with the aid of specific subgenomic probes and heteroduplex analyses, we have established that the DNA element is composed of two VL30 long terminal repeat (LTR) units, a limited subset of VL30 information adjacent to both 5' and 3' LTRs, and an enclosure of MuLV-related information that shares homology primarily with MuLV gag and pol determinants (but lacks MuLV-related LTRs). This sequence arrangement is reciprocal in nature to the recombinations between MuLV and rat VL30 that generated the genomes of the Harvey and Kirsten strains of mouse sarcoma virus and most likely is the consequence of recombination between VL30 and MuLV-related elements and the subsequent deposition of the putative recombinant DNA in the mouse genome.