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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new method for obtaining HIV-I protease was suggested. Fusion proteins composed of the N-terminal fragment of human gamma-interferon and HIV-I protease connected with (Asp)4Lys (protein I) or Asp-Pro (protein II) linkers were expressed in Escherichia coli cells. The fusion proteins were produced as insoluble inclusion bodies in the 20% yield of total cell protein. Protein I was cleaved by enterokinase. The solubility of protein I was increased by treating with Na-sulfite/Na-tetrathionate under denaturing conditions. Optimal conditions for efficient acidic hydrolysis of protein II at Asp-Pro bond were found. The hydrolysis products were separated by reversed-phase FPLC. The amount of tryptophan and cysteine residues in the enzyme obtained was estimated. The activity of HIV-I protease was determined using the chromogenic peptide. AlaArgVal NleNphGluAlaNleNH2 and a high-mol-wt substrate consisting of beta-galactosidase and a fragment of gag proteins, including p17-p24 processing site.
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PMID:HIV-I protease. Cloning, expression, and purification. 910 Mar 48

The human CD4 glycoprotein is thought to be involved at several stages of the infection process with the human immunodeficiency virus type 1. To pursue this line of investigation with CD4 deletion mutants, we combined a system of high transient cell-surface expression of the target molecule with an assay of HIV-1 infectivity based on induction of LTR-linked luciferase activity. The approach was also designed to distinguish between defects in gp120 binding and postbinding events. Optimal assay conditions were established with wild-type CD4 and the previously characterized CD4 mutant, d367-371. New deletions of CD4 domains D3 and D4 were then designed from a rat model of the D3D4 atomic coordinates with the concern of maintaining overall structural integrity. While all CD4 mutants were found to be defective towards HIV, it was demonstrated that the mutations affected different stages of the entry process. These data indicate that the system is well suited for studying the intricacy of molecular interactions involving HIV envelope glycoproteins and its receptors.
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PMID:CD4 deletion mutants evaluated for human immunodeficiency virus type 1 infectivity in a highly efficient system of expression and detection based on LTR-dependent reporter gene activation. 918 44

The mucosal surfaces represent the primary site for transmission of several viruses including HIV. To prevent mucosal transmission and dissemination to the regional lymph nodes, an effective HIV vaccine may need to stimulate immune responses at the genital and rectal mucosa. Optimal induction of mucosal immunity in general requires targeting antigens to the specialized antigen presenting cells of mucosal associated lymphoid tissues. The nasal mucosa may provide a simple, non-invasive route to deliver DNA encoding the introduced gene to stimulate mucosal immunity. As a first step to evaluate the feasibility of this approach, we have investigated as a model system, systemic and mucosal immune responses elicited to firefly luciferase generated by DNA immunization. Incorporating DNA into liposomes with cationic lipids enhanced luciferase expression in nasal tissue, and was associated with induction of a humoral response in serum and vaginal fluids and also a proliferative and cytotoxic T lymphocyte response in the spleen and iliac lymph nodes draining the genital and rectal mucosa.
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PMID:Mucosal immunization with DNA-liposome complexes. 923 23

Two different responses to the therapy were observed in a group of patients receiving the protease inhibitor indinavir. In one, suppression of virus replication occurred and has persisted for 90 weeks (bDNA, < 500 human immunodeficiency virus type 1 [HIV-1] RNA copies/ml). In the second group, a rebound in virus levels in plasma followed the initial sharp decline observed at the start of therapy. This was associated with the emergence of drug-resistant variants. Sequence analysis of the protease gene during the course of therapy revealed that in this second group there was a sequential acquisition of protease mutations at amino acids 46, 82, 54, 71, 89, and 90. In the six patients in this group, there was also an identical mutation in the gag p7/p1 gag protease cleavage site. In three of the patients, this change was seen as early as 6 to 10 weeks after the start of therapy. In one patient, a second mutation occurred at the gag p1/p6 cleavage site, but it appeared 18 weeks after the time of appearance of the p7/p1 mutation. Recombinant HIV-1 variants containing two or three mutations in the protease gene were constructed either with mutations at the p7/p1 cleavage site or with wild-type (WT) gag sequences. When recombinant HIV-1-containing protease mutations at 46 and 82 was grown in MT2 cells, there was a 68% reduction in its rate of replication compared to the WT virus. Introduction of an additional mutation at the gag p7/p1 protease cleavage site compensated for the partially defective protease gene. Similarly, rates of replication of viruses with mutations M46L/I, I54V, and V82A in protease were enhanced both in the presence and in the absence of Indinavir when combined with mutations in the gag p7/p1 and the gag p1/p6 cleavage sites. Optimal rates of virus replication require protease cleavage of precursor polyproteins. A mutation in the cleavage site that enhanced the availability of a protein that was rate limiting for virus maturation would confer on that virus a significant growth advantage and may explain the uniform emergence of viruses with alterations at the p7/p1 cleavage site. This is the first report of the emergence of mutations in the gag p7/p1 protease cleavage sites in patients receiving protease therapy and identifies this change as an important determinant of HIV-1 resistance to protease inhibitors in patient populations.
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PMID:Drug resistance during indinavir therapy is caused by mutations in the protease gene and in its Gag substrate cleavage sites. 926 88

The very long latency between HIV infection and the appearance of AIDS imposes extensive information processing requirements on partner notification efforts. The apparently contradictory needs of maintaining the right to privacy of infected persons, while simultaneously providing information to persons at risk of infection, impose severe security requirements. These requirements can be satisfied by a Contagion Management System based upon networked personal computers of a kind now becoming available. Security of information is based upon cryptographic protocols that implement anonymous partner notification (contact tracing) and Privacy-Preserving Negotiation. The proposed scheme has the properties that contact tracing is automated, contacts remain anonymous, sensitive information is kept private, and risk-conscious users act as if sensitive information was public. Optimal health protection can thus be obtained while securing informational rights.
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PMID:Automation of contagion vigilance. 929 22

A subset of CD8+ T lymphocytes that expresses CD28, a membrane receptor for B7 differentiation Ags found on APCs, is primarily responsible for the noncytotoxic suppression of HIV replication in CD4+ cells of HIV-infected individuals. Optimal inhibition of HIV production by CD8+ cells occurs after triggering the CD28 molecule on the cells with anti-CD28 Abs during stimulation. Blocking the interaction of the CD28 and B7 molecules with a CTLA4Ig fusion protein abrogates the ability of autologous macrophages to enhance this CD8+ cell antiviral activity. This blocking effect can be reversed by treating the CD8+ cells with anti-CD28 Ab. The increase in antiviral activity following CD28 costimulation correlates with enhanced IL-2 production and IL-2R expression by CD8+ cells. Prevention of IL-2 binding to its receptor, using anti-IL-2 or anti-IL-2R Abs, reduces the ability of CD8+ cells to suppress HIV replication following CD28 costimulation. Importantly, engagement of the CD28 molecule during stimulation of CD8+ cells from individuals with AIDS restored the ability of their cells to suppress HIV replication. Thus, triggering the CD28 molecule during stimulation of CD8+ cells could clinically benefit HIV-infected symptomatic patients.
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PMID:CD28 costimulation increases CD8+ cell suppression of HIV replication. 936 42

Disability assessment and rehabilitation intervention have implications for specific stages of HIV disease, with the intention of maximizing overall function and decreasing the burden of care. The AIDS epidemic has challenged communities to develop and to mobilize care networks for persons infected with HIV. A major part of that mobilization has been a push toward community and home-based services. Reliable and valid functional assessment data are necessary to evaluate HIV-related disability changes over time for patients in the hospital and at home. Epidemiologic data also hold implications for rehabilitation healthcare workers in terms of expertise in HIV-specific areas and on the staffing level. Access to rehabilitation services will need to be considered by public policymakers and financial concerns will need to be explored. Because individuals with HIV and AIDS are living longer and with greater levels of health, the chronicity of the disease warrants community support and long-term care. Various functional and quality-of-life measures can assist in the development of resources and medical interventions. As survival increases, rehabilitation professionals can anticipate more referrals for the assessment and management of physical disability in persons with HIV infection. A critical task for health service research is to ensure that HIV healthcare settings deliver optimum services at reasonable costs. Optimal care requires maximizing autonomous functioning and reducing periods of disability and dependence.
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PMID:Physical therapy management for the patient with HIV. Lower extremity challenges. 957 57

Wasting is a debilitating complication of the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and is a major cause of morbidity and mortality. The etiology of wasting in HIV/AIDS is complex and its origins are multifactorial. Both patterns of simple starvation and the more complex metabolic and endocrine alterations associated with stress and trauma have been described in patients with the AIDS wasting syndrome. Observations suggest that the pathophysiology of the wasting in individual patients with HIV/AIDS may vary according to the primary cause of wasting and underlying disease activity. Optimal treatment of the AIDS wasting syndrome will depend on a thorough evaluation of all possible contributing factors. This review addresses the pathophysiologic basis of weight loss in HIV/AIDS, based on the current literature.
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PMID:The etiology of wasting in the human immunodeficiency virus and acquired immunodeficiency syndrome. 962 88

Retroviral reverse transcriptase-associated RNase H enzymes are responsible for degradation of viral RNA, including removal of the tRNA primer after plus-strand strong-stop synthesis and cleavage of the polypurine tract primer. These activities are required for the complex viral replication and result in generation of the long terminal repeats. The human immunodeficiency virus type 1 (HIV-1) RNase H domain has been expressed independently of the polymerase domain and possesses Mn2+-dependent activity with a hexahistidine tag. The isolated domain maintains the ability to specifically remove a tRNA primer mimic. In this study, the substrate determinants for recognition of the cognate tRNA3Lys are defined. Model substrates were constructed which mimic the RNA-DNA hybrid obtained from plus-strand strong-stop synthesis. Deletion substrates containing only 12, 9, or 6 positions of the tRNA primer were capable of being cleaved by the isolated RNase H domain. Mismatch and bromodeoxyuridine mutagenesis analysis indicated that positions 2, 3, 4, and 6, when mutated, affected the specificity of RNase H activity. Substitution substrates indicated that positions 4 and 6 within the RNA primer were important for recognition and cleavage by the HIV-1 isolated RNase H domain. Moloney murine leukemia virus-HIV-1 hybrid substrates were constructed which demonstrated that changes to HIV-1 sequences at positions 4 and 6 were sufficient but not optimal for regaining cleavage by the isolated HIV-1 RNase H domain. Optimal site-specific cleavage between the terminal ribonucleotide A and ribonucleotide C requires additional sequences beyond the first six positions but less than nine.
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PMID:Sequence requirements for removal of tRNA by an isolated human immunodeficiency virus type 1 RNase H domain. 965 29

Optimal HIV-1 infectivity requires the presence of both the viral factor Nef and the cellular protein cyclophilin A (CyPA) during virion assembly. These two proteins are integral components of HIV-1 particles. Both CyPA and Nef facilitate a step in the viral life cycle occurring between penetration and reverse transcription, suggesting a common mechanism of action. Experiments were performed to test the potential interplay of Nef- and CyPA-mediated enhancement of HIV-1 infectivity. In single-cycle infection assays, nef-defective virions were partially resistant to cyclosporin A (CsA), a drug that inhibits the binding of CyPA to the HIV-1 Gag precursor and CyPA incorporation into virions. Genetic dissection of the relative contributions of Nef and the cyclophilin A-Gag interaction to HIV-1 infectivity demonstrated the independence of these two effects. Nef was not required for incorporation of CyPA into HIV-1 virions and vice-versa. Surprisingly, CyPA-deficient virions remained sensitive to inhibition by CsA, in a manner that depended strongly on the presence of a functional nef gene. These results demonstrate that Nef and CyPA act independently to render HIV-1 particles fully infectious. They further suggest that in addition to blocking the CyPA-Gag interaction, CsA can also inhibit HIV-1 replication through a novel mechanism involving suppression of Nef-directed enhancement of virus infectivity.
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PMID:Mechanistic independence of Nef and cyclophilin A enhancement of human immunodeficiency virus type 1 infectivity. 970 63


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