Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoimmune reactivity is a consequence of infection with human immunodeficiency virus (HIV). We studied serological cross-reactions of purified pooled IgG from sera of HIV-infected individuals by using nested sets of synthetic overlapping peptides duplicating the covalent structures of T-cell receptors (TCRs) and immunoglobulin light chains and report that two processes of autoantibody production occur. (i) IgG autoantibodies to putative regulatory variable domain CDR1 and FR3 epitopes (where CDR is complementarity-determining region and FR is framework region) are present in pooled IgG from HIV-infected individuals at levels 10-fold greater than that in pooled IgG from healthy humans. (ii) Anti-TCR autoimmunization involves antigenic mimicry between a conserved peptide stretch of the major neutralizing V3 loop determinant of HIV-1 gp120 and the conserved FR4 segment of the TCR V beta. Affinity-purified antibodies to the synthetic V3 loop peptide bound to a recombinant single-chain TCR and to a synthetic TCR joining segment peptide containing the FR4 sequence. Conversely, affinity-purified autoantibodies from pooled IgG from HIV-infected individuals to the TCR peptide bound the V3 loop peptide and a single-chain TCR. Inhibition studies indicated that the cross-reactive immunizing antigen was the V3 loop. These results bear upon the impact of HIV infection on immune regulation and on the selection of peptides for vaccine development.
 ...
PMID:Autoantibodies to the alpha/beta T-cell receptors in human immunodeficiency virus infection: dysregulation and mimicry. 797 73

The CDR-3 region of CD4 has been proposed to be involved in the fusion reaction between human immunodeficiency virus type 1 (HIV-1) and CD4+ cells, either at a stage involving virus binding or subsequent to virus binding. Part of the evidence for this has been the observation that monoclonal antibodies (MAbs) to CDR-3 block HIV infection potently without strongly inhibiting the binding of monomeric gp120 to CD4. Here I show that, in a system using oligomeric, virion-bound gp120, a MAb to CDR-3 resembles those to CDR-2 in that it inhibits soluble CD4 binding to virions. Consequently, ternary complexes of MAb-soluble CD4-gp120 cannot be detected with CDR-2 MAbs and are detectable only at a very low level with a CDR-3 MAb, but they clearly form when a control MAb to CD4 domain 4 is used. Although not in direct conflict with previously published data on the role of CDR-3 MAbs in the inhibition of HIV-1 infection, these experiments do not support the hypothesis that the CDR-3 region is specifically involved in virus entry at a postbinding stage.
 ...
PMID:A monoclonal antibody to the CDR-3 region of CD4 inhibits soluble CD4 binding to virions of human immunodeficiency virus type 1. 849 74

Clinicians and microbiologists will participate in voluntary national reporting of HIV infections and AIDS only if they have confidence in the scheme's confidentiality. At the same time, if the data are to be accurate, it must be possible to recognise reports that refer to the same individual. The use of surname 'soundex' code in combination with date of birth meets both requirements. We describe its use in the database of reported HIV infections held at the PHLS AIDS Centre. By the end of 1994 over 93% of the 20,407 reports on the database were soundex coded, and 70% of AIDS reports were linked to independent reports of HIV infection from microbiologists. In 1994, 22% of the reports of HIV infection were recognised as duplicating earlier reports of infection. Coding surnames using soundex is an acceptable and practical tool in surveillance of an infection for which confidentiality is a prime concern.
Commun Dis Rep CDR Rev 1995 Nov 10
PMID:'Soundex' codes of surnames provide confidentiality and accuracy in a national HIV database. 854 40

Projections of the future incidence of AIDS cases are needed for planning purposes, to help set research priorities, and to describe the most likely pattern of transmission of HIV infection in the past that underlies the observed and projected incidence of AIDS. Earlier reports of projections for England and Wales were published in 1988, 1990, and 1993. During 1995 a group of experts has worked, using AIDS case reports to the end of December 1994, to make new projections to the end of 1999. The expert group concludes that, after adjustment for underreporting, there will be between 1840 and 2300 new cases of AIDS in England and Wales in 1997, and between 1760 and 2455 new AIDS cases in 1999. For planning purposes, a figure of 2025 new AIDS cases is projected for 1997, and 2010 for 1999. The planning projections for new AIDS cases in 1997 and 1999 among the main exposure categories, after adjustment for underreporting, are as follows: homo/bisexual males 1305 and 1235, people exposed heterosexually 490 and 525, and injecting drug users 140 and 155. Between 1995 and 1999, it is expected that new AIDS cases may fall by 7% in homo/bisexual males, and rise by 25% in the heterosexual exposure category and by 29% in injecting drug users. The incidence of AIDS in the children of mothers infected with HIV is expected to rise steadily from 30 new cases in 1994 to 45 in 1997 and 55 in 1999. New cases in recipients of contaminated blood or blood factors are expected to fall to 35 in 1997 and 30 in 1999, compared with a peak 10 years earlier of over 70 new cases each year. It is projected that 4010 AIDS cases will be alive in England and Wales at the end of 1999, and that the same number of people will be alive with other forms of severe HIV disease. Since 1989 the proportion of reported AIDS cases who live in the NHS Thames regions has remained constant at between 70% and 75%. We expect this concentration of AIDS cases in the south east, particularly within London, to remain unchanged. Compared with the report published in June 1993, the planning projections for 1997 are 37% lower for cases acquired heterosexually, and the upper boundary of the range in this exposure category has fallen from 1140 to 495. The reduction in the planning projection has resulted from a substantial decline in the rate of increase in the number of new AIDS cases arising each year from heterosexual exposure. The range of uncertainty has narrowed largely because more extensive seroprevalence data are now available. For homo/bisexual males, the planning projection for 1997 has fallen by 3%, because the 1993 report presented an over optimistic view of the extent to which patients received treatment and prophylaxis before the onset of AIDS, since such management became available in 1988. Unlike the 1993 working group, the 1995 working group has access to data from several years on the uptake of treatment and prophylaxis given before the diagnosis of AIDS. It is estimated that about 21,900 adults (range 20,400 to 23,400) were infected with HIV in England and Wales at the end of 1993. This total includes 12,350 who had been infected through male homosexual exposure, 2050 men and women infected through injecting drug use, 6800 men and women infected through heterosexual exposure, and about 3000 adults alive with AIDS. Various data indicate that HIV transmission among homo/bisexual men has been substantial since 1989. Use of data from the unlinked anonymous HIV prevalence monitoring programme suggest that between 500 and 1000 HIV infections due to homosexual male exposure occurred each year in 1992 and 1993. Should HIV transmission continue at this level, a high incidence of AIDS within the homo/bisexual male community will be inevitable for many more years. Most HIV infections and AIDS cases due to heterosexual exposure are thought to have been acquired abroad. The future of the epidemic in this exposure category is therefore unclear.
Commun Dis Rep CDR Rev 1996 Jan 05
PMID:The incidence and prevalence of AIDS and prevalence of other severe HIV disease in England and Wales for 1995 to 1999: projections using data to the end of 1994. 858 Nov 17

To investigate the role of polyclonal stimulation and antigen driven selection in the pathogenesis of acquired immunodeficiency syndrome (AIDS) related lymphomas, we studied the variable region nucleotide sequence of heavy (VH) and light (VL) chains expressed by 3 Burkitt lymphomas (BL) associated with HIV infection. Two cases expressed the VH3-30P1 gene with 88.6% and 86.7% homology when compared to their germinal counterpart, whereas the VH4-18 was rearranged in the third one (89% identity). All these genes displayed high numbers of mutations (27, 22, 28 respectively), predominating in CDR regions. The encoded light chain genes determined for cases 1 and 2 expressed the same V kappa I-018 gene. These results indicate that: 1) Although, it is difficult to address the issue of VH usage based on the limited number of cases studied, Burkitt's lymphoma associated with AIDS may use a restricted repertoire of Ig genes. 2) Mutations and/or replacements predominated in CDR regions, which might suggest the occurrence of an antigen driven selection process, at least in some AIDS associated lymphomas. However, the high ratio of mutations observed in framework (FW) regions also favors the possibility that the antigen selection process is associated with polyclonal B cell stimulation.
 ...
PMID:Complete nucleotide sequence of Ig V genes in three cases of Burkitt lymphoma associated with AIDS. 862 68

A number of monoclonal antibodies have been raised against CD4, the receptor on T cells for the HIV envelope glycoprotein gp120. In the present paper we describe biological activities and sequence analysis of seven CD4 MAb. Five of these MAb preparations compete with HIV/gp120 for CD4 binding. The sequences of the variable regions for these MAb were determined in order to ascertain any correlation with selective V gene usage. A relationship was found between the expressed variable region genes and the CD4 recognition pattern. The VH genes that are used can be subdivided into two major groups expressing either a VH gene belonging to the J558 family or to the VGam family. The usage of the VL genes varies, indicating that the epitope specificity is predominantly determined by the rearranged VH genes. The distinct cross-reactivity pattern of these MAb also correlates with their capacity to block binding of recombinant gp120 to CD4 in vitro. Although five of these MAb were able to block gp120 binding none of the CDR sequences shows a relevant homology to the gp120 sequence. This indicates a steric hinderence mechanism for blocking gp120 binding and not a direct interaction with the receptor binding site on CD4. The data also confirm the failure of these MAb as a potential target for receptor mimicry.
 ...
PMID:Structural diversity of monoclonal CD4 antibodies and their capacity to block the HIV gp120/CD4 interaction. 874 91

A considerable part of the Ab repertoire is given over to polyreactive Abs capable of interacting with multiple antigenic species. Neither the function of these Abs nor the molecular basis for their activity is known. To address the latter problem, we have compared the amino acid sequences of a large panel (n = 70) of polyreactive human monoclonal Fab fragments and conducted a series of engineering experiments on a prototype polyreactive Fab. The Fab fragments were retrieved from combinatorial IgG libraries prepared from the bone marrow of long term asymptomatic HIV-1 seropositive donors. The general features displayed by the panel of IgG polyreactive Abs include 1) skewed VH family usage with a predominance of VH1 and VH4 clones and a paucity of the normally prevalent VH3 family; 2) use of a variety of different VH germ-line genes within the context of the family usage and no restriction in D or JH gene usage; 3) skewed VL gene usage: 75% of Fabs used one of two germ lines; and 4) extensive somatic modification of both heavy and light chains. The importance of the heavy chain, in particular the heavy chain CDR3 (HCDR3), in dictating the polyreactive phenotype was demonstrated for the prototype Fab by chain shuffling and CDR transplantation experiments. in addition, and most strikingly, a constrained peptide based on the HCDR3 sequence was shown to be polyreactive and to inhibit binding of the parent Ab to a panel of Ags. A role for conformational flexibility in polyreactivity was suggested by a marked temperature dependence of Ab recognition of Ag. One Ab was shown to be polyreactive at 37 degrees C, but was apparently monoreactive at 4 degrees C. We hypothesize that Ab polyreactivity is associated with conformationally flexible HCDR3 regions in the context of certain favorable framework configurations.
 ...
PMID:Determinants of polyreactivity in a large panel of recombinant human antibodies from HIV-1 infection. 875 24

The role of the CDR-3-like loop of the first domain of the CD4 molecule in infection by the human immunodeficiency virus type 1 (HIV-1) is controversial. In an attempt to determine whether the strong negative charge in the CDR-3-like loop influences HIV-1 infection we have substituted by mutagenesis negative for positively charged residues at position 87/88 and 91/92. These mutations were shown to have no obvious effect on CD4 conformation outside of the CDR-3-like loop. Infection of cells expressing the E87K/D88K substitution mutant resulted in a selective reduction in infectivity for certain HIV-1 viruses compared to cells expressing wile-type CD4. Viruses Hx10, HxB2, and MN were 4- to 13-fold less efficient at infecting the E87K/D88K mutant, whereas SF2, RF, and NDK yielded an efficiency of infection similar to, or slightly greater than, that of the wild type. To investigate the step at which infectivity was selectively reduced, we compared early events in the life cycles of Hx10 and SF2 viruses using PCR entry and gp120-binding assays. Both gp120 binding and virus entry were reduced for Hx10 on the mutant CD4-expressing cells as compared to wild-type CD4-expressing cells, whereas no difference was seen in either assay with SF2. Although relatively small in magnitude, the contribution of the CDR-3-like loop to the overall CD4-gp120 interaction may serve to modify the binding and entry of certain virus isolates.
 ...
PMID:Selective effects of electrostatic changes in the CD4 CDR-3-like loop on infection by different human immunodeficiency virus type 1 isolates. 882 16

Differences in kinetics of infection, cellular tropism, and cytopathology of SIV and HIV appear to depend on both viral and host factors. We investigated the role of critical CD4 structures from African green monkeys (AGM) a natural SIV host, from pig-tailed macaques (PT) an unnatural SIV host, and from humans, as well as the role of species-specific cellular factors involved in the tropism, kinetics of infection, and cytopathic effects of several SIV and HIV-1. Critical regions of the PT macaque and AGM CD4 genes (V1, V1J1, and V1J1V2J2) were stably expressed as chimeras with the human CD4 gene in human (HeLa and 293) and macaque (CMMT) cell lines. CD4 expressing cell lines were used for infection studies with cell-free SIVsm, SIVmac, SIVsmmPBj, SIVagm, and HIV-1. Results show that both PT CD4 and AGM CD4 supported infection with comparable infection kinetics by all SIV or HIV-1 strains tested. Although structural analysis predicted a major change in secondary structure of AGM CD4/CDR-3, these structural changes did not influence the degree of syncytia formation induced by several SIV and HIV-1. However, the cell line used to express the CD4 gene appeared to be a critical determinant of infection. Thus, SlV strains did not infect human cell lines regardless of the CD4 expressed in these cells. In contrast, HIV-1 did not infect any macaque cell line. This study demonstrates that the differences in CD4 structure among different primate species are clearly not responsible for differences in SIV and HIV infection kinetics, tropism, and cytopathology. However, species-specific factor(s), presumably expressed on the cell surface, markedly influences the ability of SIV or HIV to infect cells expressing CD4.
 ...
PMID:Receptor function of CD4 structures from African green monkey and pig-tail macaque for simian immunodeficiency virus, SIVsm, SIVagm, and human immunodeficiency virus type-1. 883 65

Liposomes can be targeted to HIV-infected cells by either reconstituting transmembrane CD4 in the membrane or covalently coupling soluble CD4 to modified lipids. We investigated whether synthetic peptides could be used as ligands for targeting liposomes. A synthetic peptide from the complementarity determining region 2 (CDR-2)-like domain of CD4 could bind specifically to HIV-infected cells and mediate the binding of peptide-coupled liposomes to these cells. A peptide from the CDR-3-like domain of CD4 inhibited HIV-induced syncytia formation, but failed to target liposomes to infected cells. This apparent discrepancy may be due to the requirement for a conformational change in the CD4 receptor for the CDR-3 region to interact with the HIV envelope protein. Our results demonstrate the feasibility of using synthetic peptides to target liposomes containing antiviral drugs to HIV-infected cells.
 ...
PMID:Targeting of liposomes to HIV-1-infected cells by peptides derived from the CD4 receptor. 888 17


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>