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

The human immunodeficiency virus type 1 (HIV-1) Rev protein is a positive posttranscriptional regulator of viral structural gene expression and essential for virus replication. Rev mediates its effects through interaction with an RNA target sequence, the Rev responsive element (RRE), present within the env mRNA. Previous studies have shown that the basic stretch of amino acids are required for Rev's ability to bind RNA, whereas residues present near the carboxy terminus are essential for full biological activity. Deletion mutagenesis was used to define the minimal domain required for RNA binding and function. We found that amino acids 8 through 67 confer full binding activity, whereas full biological activity requires the presence of residues 8 through 83. The minimal RNA binding sequence of HIV-1 Rev also interacts and functions with the HIV-2 and SIV RRE elements, indicating that the same domain is responsible for the biological activity with different, but related viruses. Mutational analysis of the RRE was also carried out in an effort to further define elements crucial for its function. Our findings indicate that interaction with Rev involves a stretch of three G nucleotides present at the base of a stem loop structure previously shown to be critical for Rev binding. These results suggest that the high degree of secondary structure of the RRE RNA may serve as a guide to bring Rev in contact with a primary nucleotide sequence required for stable protein-RNA association.
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PMID:Mutational analysis of the HIV-1 Rev protein and its target sequence, the Rev responsive element. 202 97

The structural variability of the external glycoproteins of primate immunodeficiency viruses, has, so far, been investigated exclusively by sequence comparison of the respective proviral genomes. We have examined the structural relationship amount the external glycoproteins from three specific human immunodeficiency viruses (HIF-1, HIV-2), three specific simian immunodeficiency viruses from macaques (SIVmac) and three specific SIV from African green monkeys (SIVagm) by peptide mapping. Differences among glycoproteins were most pronounced between HIV-1 and SIVmac, as well as HIV-2. Two specific glycoproteins from independent SIVagm isolates were closely related to HIV-1, whereas the glycoprotein from a third SIVagm isolate was more similar to those of SIVmac and HIV-2. Our analysis reflects the classification of primate immunodeficiency viruses into three groups, the HIV-2 and SIVmac viruses, the green monkey isolates and HIV-1.
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PMID:Structural comparison of the external glycoproteins of human and simian immunodeficiency virus. 204 May 88

A vaccine against HIV is badly needed. In the average clinical situation the virus displays a low-rate capacity to transfer infection. The frequency is significantly below 1 per contact situation, that is, a single infectious unit is the normal cause of infection. The time to induce disease in the adult is between 5 and 10 years. These facts are considered positive in relation to producing an HIV vaccine to achieve sterilizing and/or protective immunity. A summary of animal and human HIV/SIV vaccine studies is made giving certain support for the prospects of producing an HIV vaccine.
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PMID:Prospects for an HIV-vaccine. 206 89

Peptides 12-25 amino acids in length from the V1J1 region of the CD4 molecule (residues 1-120) were synthesized as randomly derivatized, deliberately derivatized, or pure peptide products, and tested for their ability to inhibit HIV-1-induced cell fusion, HIV-1 and SIV infection of CD4-positive human cells, HIV-1 envelope glycoprotein binding to the CD4 molecule, CD4-neutralizing antibody binding to the CD4 holoreceptor, and CD4-dependent cellular immune function in the mixed lymphocyte and cytotoxic T-cell bioassays. Only peptides derived from the complementarity-determining region 3 (CDR3)-homologous domain of CD4, in particular CD4(81-92) and CD4(81-101), were effective antiviral agents. Within the CD4(81-92) series, R-group derivatization of selective amino acid residues was an absolute requirement for biological activity. The prototype compound T1C4E5-tribenzyl-K10-acetyl-TYICEVEDQKEE inhibited HIV-1-induced cell fusion at 32 microM, HIV-1 infection of CEM-SS cells at 10 microM, SIV infection of CEM-174 cells at less than 125 microM, gp120/CD4 binding at 60 microM, and postinfection cell-mediated viral transmission at 10-15 microM. Compounds of identical structure and derivatization, but of altered primary sequence, were substantially less active, or without activity, in these assays. These data indicate that the effect of amino acid derivatization of the CD4(81-92) peptide was most likely restriction of the flexible underivatized peptide backbone to a conformation closely approximating that of the CDR3-homologous gp120 binding site of the native CD4 molecule. Peptide antiviral activity was specific, as judged by lack of cytotoxicity, lack of inhibition of HTLV-1-induced cell fusion, and lack of inhibition of CD4-dependent cellular immune function in vitro. Further derivatization of the prototype compound involving the production of cyclic congeners yielded peptides with submicromolar potency to block HIV-1 infection, strengthening the hypothesis that previous peptide derivations accomplished partial restriction of the conformation of CD4(81-92) to one favorable for interaction with gp120. Concentrations of the original prototype compound T1C4E5-tribenzyl-CD4(81-92) that inhibited infection in vitro more than 50% could be achieved for several hours by intravenous infusion in primates and were well-tolerated at these levels. The peptide was not efficacious to inhibit establishment of viral infection at these doses; however, peptide treatment did lower average viral antigenemia and delay the cumulative time to morbidity relative to the control group.
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PMID:Peptides derived from the CDR3-homologous domain of the CD4 molecule are specific inhibitors of HIV-1 and SIV infection, virus-induced cell fusion, and postinfection viral transmission in vitro. Implications for the design of small peptide anti-HIV therapeutic agents. 207 14

Neither vaccine nor therapy are, to date, available against human HIV infections. Because few is known on human pathogenesis, a standardized animal model is urgently required. Today, different models have been available: 1) "partial models" of the human infection (murine retrovirus, infection of SCID or transgenic mice with HIV, sheep infection with Visna, rabbits infected with HIV1, etc.). These models cannot be used in testing vaccine strategies, but may help in evaluating some particular stages of the pathogenesis of the disease, and the targets of antiretroviral drugs. 2) Disease models, such as cats infected with FIV, and, above, primates infected with HIV or SIV (SIV infected macaques, and, perhaps, HIV2 rhesus monkeys). Primate models are the only possibility to day in testing vaccine procedures before screening among a large population of seronegative humans, and determining drug combination which might be useful in HIV specific therapy. The best primate model is today the SIVMAC251 infected rhesus monkey model, which standardization is now on progress.
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PMID:[Primates as a model for the study of lentiviruses and AIDS]. 211 Jun 47

The development of a vaccine against HIV meets with considerable difficulties. The virus shows considerable genetic variability. Neutralizing antibodies raised against one HIV-1 isolate do not cross-neutralize other HIV-1 isolates. HIV can also spread directly from cell to cell without entering extracellular fluids, thus escaping neutralization. It can remain latent in the body for long periods of time, probably as an integrated provirus in the genome of the host cell. Moreover, the HIV envelope glycoprotein appears to be poorly immunogenic for primates. It elicits only weak neutralizing antiviral antibody titers, perhaps due to epitopic suppression. Preliminary data suggest, however, that neutralizing antibodies might be protective, and there is evidence from work with SIV that certain types of vaccines might induce protection against infection. These findings foster the hope that it will eventually be possible to develop a HIV vaccine.
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PMID:Prospects for an AIDS vaccine. 211 87

In summary, HIV vaccine studies described have generally not been designed to measure the effect of the adjuvant or to make comparisons between adjuvants. In only one study was a head-to-head comparison made between HIV antigen alone and antigen formulated with different adjuvants. We hope that future experiments with HIV/SIV vaccine candidates will be designed to determine the relative potency and safety of different adjuvants. Unfortunately, such experiments tend to be tedious and expensive. The design of these studies will need to address a number of variables which influence the response to the vaccine, including route and schedule of immunization, genotype and species of the vaccinated subject, and intrinsic characteristics of the antigen. In addition, the immunologic endpoints should include measurement of both B and T cell function. The carrier/adjuvant/antigen formulation should be hand-tailored and then standardized so that it is manufactured reproducibly without producing different biological effects between lots, and the vaccine formulation should be stable on storage and shipping. Finally, we obviously need to identify and test the protective antigen or antigens. The best adjuvant will never correct the choice of the wrong epitope.
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PMID:Adjuvants. 213 79

Over the past year significant progress has been made in mapping those regions of the HIV-1 envelope glycoproteins involved in virus neutralization and virus enhancement. These functional, antigenic domains of the gp160 are illustrated in Fig. 1. The role of neutralization in vaccine development is still unresolved, although high-titer antibody to the V3 loop of HIV-1 appears to be correlated with the ability to prevent HIV-1 infection by the homologous strain in chimpanzees. Therefore, the mechanism of type-specific neutralization of HIV appears to be clearly defined. The problem of group-specific neutralization of HIV-1 is still a mystery. Nevertheless, the finding that secondary structure is important for the generation of group-specific neutralizing mAbs and that carbohydrate is an important determinant for group-specific neutralization suggests that non-linear determinants are important. Answers to the question of group-specific neutralization should be available in the next few years. The role of HIV-1-enhancing antibodies in pathogenesis is not well understood. Nevertheless, the ability of patient serum to only enhance the patient's own isolate and not neutralize that isolate suggests that enhancing antibodies are important. Furthermore, the findings that enhancing antibody titers increase in SIV infection and peak immediately prior to the death of the animal suggests that such antibodies may play a role in SIV pathogenesis. With the identification and domain mapping of enhancing hu-mAbs, it should be possible to evaluate directly the role of enhancing domains in HIV and SIV pathogenesis by challenging animals in the presence of pure enhancing antibody. Only when these experiments are performed will it be possible to evaluate what role, if any, enhancing antibodies play in HIV pathogenesis. The above questions, when answered, are likely to provide important insights into lentivirus pathogenesis and help researchers to produce a safe and effective anti-HIV vaccine.
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PMID:Neutralization and enhancement of in vitro and in vivo HIV and simian immunodeficiency virus infections. 215 61

Scientific progress on the measurements and biological significance of neutralizing antibodies to HIV and SIV was discussed at a WHO Workshop held at the WHO Collaborating Centre on AIDS at the National Institute for Biological Standards and Control in London, on 3-5 October 1988. The Workshop was attended by 32 experts from eight countries. The subjects discussed at the workshop were: (1) systems for measurement of neutralizing antibodies; (2) reference reagents and comparative studies of neutralizing assays; (3) epitope characterization; (4) mechanisms of neutralization; (5) role of neutralizing antibodies in vivo and their correlation with disease status and progression. It was stated that accurate and reproducible measurement of HIV neutralization is important to studies of HIV immunobiology, characterization of HIV strains and vaccine development. Several different techniques of neutralizing antibody measurement have been developed, but further studies are required to compare and evaluate these methods. The biological significance of neutralizing antibodies and mechanism of neutralization is not yet well understood. The available data indicate that neutralizing antibodies may be either strain-specific or more broadly reactive within the HIV-1 group. To evaluate reproducibility and variability of different neutralizing antibody assays two international collaborative studies were undertaken. The results of these studies showed that though there was good general agreement in the detection of neutralizing antibodies by diverse assays, variation in this quantitation was found. It was concluded that further standardization is needed. Data presented showed that HIV neutralizing antibodies are produced in natural human infection and in animal models, but no correlation has yet been demonstrated between neutralizing antibody titres and progression to disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Report of a WHO workshop on the measurement and significance of neutralizing antibody to HIV and SIV. London, 3-5 October 1988. 216 71

The measurement of cell-mediated immunity against the etiologic agent of human AIDS (HIV) in the non-human primate model of AIDS (simian immunodeficiency virus, SIV) has been difficult. In general, culture of peripheral blood mononuclear cells from HIV-1- and SIV-infected humans and monkeys, respectively, with purified inactivated HIV and SIV virus preparations has given inconsistent or negative proliferative responses. However, we describe herein an assay which consists of coculturing monocytes that have been pulsed with inactivated SIVsmm with nylon-wool-purified autologous T cells, leading to antigen-specific T-cell proliferation. The proliferative response, which predominantly occurs in CD4+ T cells, is major histocompatibility complex (MHC) class II-restricted and requires antigen processing. This assay will greatly facilitate the identification of the immunodominant epitopes recognized by T cells in sooty mangabeys, which are naturally infected but remain clinically asymptomatic, and in rhesus macaques, in which experimental infection leads to clinical symptomatology similar to human AIDS, eventually resulting in death.
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PMID:Requirements for simian immunodeficiency virus antigen-specific in vitro proliferation of T cells from infected rhesus macaques and sooty mangabeys. 216 18


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