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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations were made by recombinant DNA techniques in an infectious molecular clone of the human immunodeficiency virus San Francisco isolate 2 (HIVSF2) [formerly the prototype isolate of the acquired immunodeficiency syndrome-associated retrovirus (ARV-2)]. The effect of these changes on the replicative and cytopathologic properties of the virus was studied by transfecting modified virus clones into cultured human cells. Mutations in the gag, pol, env, and tat regions precluded virus replication and cytopathology in lymphoid cells. A mutation in orf-A dramatically reduced but did not abolish virus replication. Mutant viruses with deletions in the orf-B region were highly cytopathic and replicated to approximately 5-fold higher levels than wild-type virus. They also produced approximately 5-fold more viral DNA in infected lymphoid cells than did wild-type virus. Thus, the orf-B region may function to down-regulate virus replication. This mutational analysis of the HIVSF2 genome is a means of assessing genes regulating viral replication and cytopathology.
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PMID:Mutational analysis of the human immunodeficiency virus: the orf-B region down-regulates virus replication. 243 56

The only animal that can be reproducibly infected with HIV, and that thus provides an experimental system for testing the effectiveness of prototype vaccines, is the chimpanzee. We compared proliferative responses to HIV and to vaccinia virus (VV) antigens of lymphocytes taken at various times from chimpanzees vaccinated with recombinant VV expressing different HIV genes. Animals were immunized with the original VV strain, as control, or with constructs expressing gp160 (VV160) given exclusively or in combination with one or two other constructs producing p25 (VV25), F/3'-orf (VVF), or the human interleukin-2 (IL-2) gene, which was included in an attempt to amplify immune responses. Irrespective of the HIV gene utilized, lymphocyte proliferation to HIV was usually weak and rapidly decreased after each inoculation, contrasting with strong and sustained responses to VV. Lack of adequate recall reactivity after challenge with fixed autologous lymphocytes expressing VV-produced HIV antigens indicated that vaccination resulted only in low levels of HIV-specific memory cell priming. The use of IL-2-producing VV did not lead to increased responsiveness. Reactivity to soluble purified gp160, but not to p25, could be detected in PBL from animals that had received both VV160 and VV25, while immunization with VVF resulted in a significant response to this protein in one of two animals. The transient nature of T cell reactivity to HIV might explain why, in similar studies, chimpanzees were not protected from infection with live HIV.
AIDS Res Hum Retroviruses 1989 Feb
PMID:Cell-mediated immune proliferative responses to HIV-1 of chimpanzees vaccinated with different vaccinia recombinant viruses. 247 Mar 98

Human immunodeficiency virus type 1 (Z321 designate, HIV-1Z321), the oldest known HIV, was isolated from a serum sample collected in Zaire in 1976 and was molecularly cloned. Restriction enzyme analysis of unintegrated viral DNA revealed the presence of conserved restriction enzyme cleavage sites in the long terminal repeat sequences. Nucleotide sequence analysis of the 3' end of the viral DNA revealed a pattern similar to other HIV-1 isolates described. However, some of the common restriction sites present in other isolates were absent in HIV-1Z321. The extent of differences between HIV-1Z321 and recent isolates from North America and Zaire was 17.86-18.36% on the nucleotide sequence level and 26.5-33.2% difference in the predicted amino acid sequence in the envelope gene. Differences were also noted in 3'-orf (nef: according to HIV gene nomenclature; see Ref. 42) gene and U3 region of the long terminal repeat sequences of HIV-1Z321 and other isolates. Nucleotide sequence of a HIV-1 isolate, 12 years apart from the present isolates, will provide an important time calibration point for the evolutionary divergence of HIV isolates. Hybrid HIV was also generated by transfecting HIV-1Z321 and HIV-1HTLV-III viral DNAs into cells.
AIDS Res Hum Retroviruses 1989 Apr
PMID:Molecular characterization of HIV-1 isolated from a serum collected in 1976: nucleotide sequence comparison to recent isolates and generation of hybrid HIV. 271 63

Eight coding regions designated gag, pol, env, sor, R, tat, art/trs, and 3' orf have been identified in the genome of the human immunodeficiency virus type 1 (HIV-1). Several other open reading frames have the potential to encode additional viral proteins. In this study, we show that HIV-1 has another coding sequence whose product is expressed during natural infection. Unlike antibody to other HIV-1 proteins, the prevalence of antibody to the product encoded by this region is elevated in patients with acquired immune deficiency syndrome (AIDS). Because no analogous coding region has been identified in HIV-2, the antibody to the product of this coding region may serve as a marker to distinguish infection with HIV-1 from infection with HIV-2.
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PMID:Human immunodeficiency virus type 1 has an additional coding sequence in the central region of the genome. 284 97

The human spumaretrovirus (HSRV) isolated from a nasopharynx carcinoma patient 17 years ago has a RNA genome 11 kb in size. It encodes besides the gag, pol, and env genes several novel genes (S1 and bel 1, 2, and 3) that are comparable to the regulatory genes R, X, tat, art, and 3'-orf of the human (HIVs) and simian immunodeficiency viruses (SIVs) with respect to genomic location and to sizes of the putative gene products. A comparison between the HIV protein sequences of the pol and the novel genes to the corresponding gene product sequences of HSRV revealed that HSRV is related to the lentiviruses but occupies a distinct phylogenetic placement of its own. A detailed analysis of the reverse transcriptase domain allows the construction of a phylogenetic tree for the known retroviral subfamilies and/or groups, including the oncoviruses, the lentiviruses, the spumaviruses, the HLTV-BLV group, and the D-type viruses. Regions of the putative novel HSRV gene products with segmental protein sequence homology to the regulatory protein of other human retroviruses are discussed. The results strengthen the view that HSRV and its novel genes should be studied in comparison to the new genes of acquired immunodeficiency syndrome (AIDS) viruses and human T cell leukemia viruses (HTLV).
AIDS Res Hum Retroviruses 1988 Dec
PMID:Genomic organization of the human spumaretrovirus and its relatedness to AIDS and other retroviruses. 285 7

The genetic diversity of the human immunodeficiency virus (HIV) isolated from transfusion-associated AIDS patients has been examined. Restriction enzyme mapping studies of integrated proviral DNA of donor and recipient origin demonstrated genomic variation between isolates. Analysis of the molecularly cloned viral genomes of one donor-recipient pair showed that virus from the recipient had restriction enzyme site differences from the donor, noticeably clustered in the env and orf-2 regions, and also had a greater number of restriction sites in common with the donor as well. These results suggest that HIV may undergo genomic variation in vivo. Comparison of donor-recipient viruses may further the understanding of the molecular basis for AIDS pathogenesis.
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PMID:Transfusion-associated AIDS: donor-recipient human immunodeficiency virus exhibits genetic heterogeneity. 288

The genome of the virus associated with the acquired immune deficiency syndrome (AIDS), human T-lymphotropic virus type III (HTLV-III), includes two open reading frames, not found in other retroviruses. One of these, designated 3' open reading frame (3'orf) is 648 base pairs (bp) in length, and overlaps with the 3' long terminal repeat (LTR) sequences. Sequences of additional HTLV-III clones were determined in order to estimate the level and location of variation within 3'orf, to gain some insight into the function of its protein product. Newly determined sequences are reported for 3'orf of two unintegrated clones of HTLV-III and three cDNA clones made from virion RNA derived from the same cell line infected with pooled blood samples of different patients with AIDS or AIDS-related complex symptoms (ARC). In addition, sequences for 3'orf were derived from an unintegrated viral clone derived from a different cell line infected with a distinct isolate from a single patient. These sequences are compared to those previously reported for six other viral clones. Sequences of 3'orf differ among clones by 1.1-10.4% bp and 2.4-17.0% of predicted amino acids. This represents significantly greater sequence variation than is found in the entire genome on average. Moreover, a functional proviral clone has a termination codon at amino acid residue 124 of this open reading frame. This raises questions concerning the structure, and regulation of expression of the protein encoded by 3'orf.
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PMID:Polymorphism of the 3' open reading frame of the virus associated with the acquired immune deficiency syndrome, human T-lymphotropic virus type III. 299 15

Studies of the genomic structure of human T-lymphotropic virus type III (HTLV-III) and related viruses, implicated as the causal agent of acquired immune deficiency syndrome (AIDS), have identified a sixth open reading frame in addition to the five previously known within the genome (gag, pol, sor, env and 3'orf). This gene, called tat-III, lies between the sor and env genes and is able to mediate activation, in a trans configuration, of the genes linked to HTLV-III long terminal repeat (LTR) sequences. We now present evidence that the product of tat-III is an absolute requirement for virus expression. We show that derivatives of a biologically competent molecular clone of HTLV-III, in which the tat-III gene is deleted or the normal splicing abrogated, failed to produce or expressed unusually low levels of virus, respectively, when transfected into T-cell cultures. The capacity of these tat-III-defective genomes was transiently restored by co-transfection of a plasmid clone containing a functional tat-III gene or by introducing the TAT-III protein itself. As HTLV-III and related viruses are the presumed causal agents of AIDS and associated conditions, the observation that tat-III is critical for HTLV-III replication has important clinical implications, and suggests that specific inhibition of the activity of tat-III could be a novel and effective therapeutic approach to the treatment of AIDS.
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PMID:The trans-activator gene of HTLV-III is essential for virus replication. 300 95

Human T-lymphotropic virus type III or lymphoadenopathy associated virus (HTLV-III/LAV) is the cause of acquired immune deficiency syndrome (AIDS). In addition to the conventional retroviral genes involved in virus replication, namely, gag, pol, and env genes, DNA sequence analysis of HTLV-III genome predicted two additional open reading frames termed by us short open reading frame (sor) and 3' open reading frame (3' orf). Furthermore, functional analysis revealed another gene with transactivating function, termed tat. We have now structurally identified and functionally characterized these HTLV-III specific genes by way of cDNA cloning. DNA sequence analysis of the clones shows that the tat and 3' orf genes contain three exons and their transcription into functional mRNA involves two splicing events and that the sor gene contains at least two exons. In vitro transcription and translation of the cloned spliced sequences show that the sor, tat, and 3' orf genes code for polypeptides with apparent mobility of 24-25 kDa, 14-15 kDa, and 26-28 kDa, respectively. All three polypeptides are immune reactive and are immunogenic in the natural host. The results demonstrate that the three extra open reading frames of HTLV-III, two of which are unique to HTLV-III, are in fact genes that function in vivo and further allow the identification of three new and previously unrecognized HTLV-III antigens with differential immunogenicity in individuals with acquired immune deficiency syndrome and related disorders.
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PMID:Three novel genes of human T-lymphotropic virus type III: immune reactivity of their products with sera from acquired immune deficiency syndrome patients. 300 54

The genome of human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV), the infectious agent etiologically associated with the acquired immunodeficiency syndrome, contains, in addition to the genes for the polymerase, core, and envelope proteins, several open reading frames. To investigate whether the 3' open reading frame (3' orf) located between the envelope gene and the 3' long terminal repeat is a gene expressed in vivo in infected individuals, we inserted a fragment of 3' orf in a prokaryotic expression vector. The protein product synthesized in bacteria was purified and allowed to react with sera from individuals infected with human T-cell lymphotropic virus type III as indicated by seropositivity for other viral proteins. Two-thirds of the sera, regardless of the clinical status of the individuals, reacted with the purified protein indicating that 3' orf is a viral gene the product of which is immunogenic in vivo. A polyclonal rabbit antiserum reacting against the 3' orf gene product was obtained by serial injection of rabbits with the purified bacterial protein. The antiserum recognized a 27-kDa protein in the human T-cell lymphotropic virus type III-infected lymphocytes.
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PMID:Expression of the protein encoded by the 3' open reading frame of human T-cell lymphotropic virus type III in bacteria: demonstration of its immunoreactivity with human sera. 301 41


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