A tumor cell line was derived from the fibrosarcoma of a 35‐year‐old Caucasian man who died without having received chemotherapy or radiotherapy. The in vitro growth properties and transplantability into antithymocytic sera treated mice were characteristic of these malignant cells. An aberrant karyology with marker chromosomes was present. No virus particles were detected.

Both the risk of the progression of HIV disease and the efficacy of antiretroviral therapy are strongly associated with the plasma level of HIV RNA and with the viral phenotype. The changes in the plasma concentration of HIV RNA predict the changes in CD4 cell counts and survival after treatment with reverse-transcriptase inhibitors.

Drug resistance conferred by specific human immunodeficiency virus type 1 (HIV-1) pol gene mutations has been associated with clinical progression in HIV-infected patients receiving anti-retroviral therapy. This study examined drug susceptibilities and pol mutations of HIV-1 strains from patients treated for 1 year with zidovudine, didanosine (ddI), or zidovudine and ddI. Ten (42%) of 24 patients receiving combination therapy versus 8/26 (31%) receiving only zidovudine had HIV-1 strains with phenotypic zidovudine resistance or a zidovudine resistance pol mutation at codon 215 (P = .6). In contrast, a ddI resistance mutation at codon 74 was less common among patients receiving combination therapy (2/24) than among those receiving ddI only (17/26; P < .001). Two patients receiving combination therapy developed resistance to zidovudine and ddI; they had HIV strains with amino acid mutations at codons 62, 75, 77, 116, and 151. Combination therapy with zidovudine and ddI selects for zidovudine-resistant HIV-1 strains lacking a ddI resistance mutation and for multidrug-resistant strains containing novel pol mutations.

Using nonstringent annealing conditions and a 2.75-kilobase segment of cloned African green monkey DNA that specifically hybridizes to the proviruses of AKR'ecotropic murine leukemia virus (MuLV) and baboon endogenous virus (BaEV) as a probe, we detected related sequences in three different preparations of human brain DNA fragments. The blot-hybridization pattern obtained with cleaved human DNA was similar to that previously reported for the interaction of MuLV cDNA and cleaved mouse DNA and suggested the presence ofnumerous copies of retrovirus-related sequences in the human genome. The labeled 2.75-kilobase fragment derived from cloned monkey DNA was used to screen a human DNA library in Charon 4A. One clone obtained hybridized to three contiguous MuLV-and BaEV-reactive fragments of the cloned monkey DNA and to multiple fragments of human DNA including a prominent 1.0-kilobase EcoRI fragment also present in the clone.In the mouse, certain endogenous type C proviruses have been shown to be vertically transmitted (1-3), have been mapped to specific chromosomal loci (4-6), and have the potential ofbeing expressed as infectious ecotropic and xenotropic (7) murine leukemia viruses (MuLV). Comparison ofresults from nucleic acid hybridization experiments, which indicate the existence of numerous copies of endogenous mouse proviruses (8-10), with those derived from genetic andvirus isolation studies, which point to a few defined inducible loci in the genomes of certain inbred mouse strains (4-6, 11), strongly suggests that the majority of the MuLV-reactive sequences in mouse DNA consist ofincomplete viral DNA segments whose function is unknown.Type C endogenous retroviruses have also been recovered from several different Old World monkeys including the baboon (12), stump-tail macaque (13), rhesus (14), and colobus (15 We recently. reported the molecular cloning of a 17-kilobase (kb) segment from African green monkey (AGM) DNA which had nearly 5 kb of homology with AKR ecotropic MuLV DNA (21). In the present manuscript we show that the internal organization of the endogenous type C AGM and baboon provi:-ruses, including 8 of 10 restriction enzyme cleavage sites, hasbeen highly conserved. Furthermore, by using a radiolabeled. 2.75-kb BamHI fragment ofthe cloned ACM-DNA, which specifically hybridizes to a similarly sized BamHI fragment (22) of the BaEV provirus, hybridization to several bands in three different restricted preparations of human DNA was observed. Based on our ability to detect type C virus-related sequences in human DNA, we cloned an 11-kb segment from human DNA which hybridizes to AGM and mouse proviral DNAs.MATERIALS AND METHODS Preparation and Cleavage ofCellular DNA. High molecular weight AGM and rhesus monkey liver DNAs were purified from fresh tissue as described (23). Baboon cellular-DNA was prepared from a cell line (CP 21) established from primary skin fibroblasts. DNA was isolated from three human brain specimens as outlined (24). Cellular DNAs were digested with restriction enzymes, ele...

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