Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-two hybridoma clones producing monoclonal antibody (MAb) against HIV-2[GH-1] were established from mice immunized with NP-40-disrupted purified whole virus of a Ghanaian isolate of human immunodeficiency virus type 2 (HIV-2), strain HIV-2[GH-1]. Of these 32 MAbs, 20 reacted with p26 and the other MAbs recognized p15 of the HIV-2[GH-1] isolate. From the results of serological characterization by these MAbs, p26 and p15 were identified as capsid proteins and matrix protein, respectively, of HIV-2[GH-1] gag products. In addition to two gag proteins, a 55-kD protein corresponding to the primary translational product of gag gene and 39-kD protein corresponding to an intermediate product of cleavage of p55 were recognized by these MAbs in the lysate of HIV-2[GH-1]-infected cells. Moreover, these MAbs were used to analyze the number of antigenic epitopes on p26 and p15 of HIV-2[GH-1] isolate. The results of cross-reactivity with different HIV-1, HIV-2, and simian immunodeficiency virus (SIV) isolates and competitive binding assay suggest that there are at least four and five antigenic epitopes in p26 and p15, respectively, of the HIV-2[GH-1] isolate. The biological activity of MAbs was studied by performing syncytium inhibition assay and infection inhibition assays. However, our MAbs could not inhibit syncytium formation and infection by cell-free virus.
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PMID:Multiple antigenic epitopes expressed on gag proteins, p26 and p15, of a human immunodeficiency virus (HIV) type 2 as defined with a library of monoclonal antibodies. 169 78

We established seven hybridoma clones producing monoclonal antibodies (MAbs) against the envelope transmembrane protein (TMP) of a Ghanian isolate of human immunodeficiency virus type 2 (HIV-2[GH-1]) from mice immunized with the detergent-disrupted purified whole virus. The MAbs were found to react with 35 kilodalton (kD) TMP of the HIV-2[GH-1] virus in a Western blot assay (WB). Two of these MAbs recognized 135 kD proteins in addition to TMP in the lysate of HIV-2[GH-1]-infected cells. Two other MAbs cross-reacted with viral components corresponding to TMPs of HIV-2ROD and SIVMAC isolates in a Western blot. Results of competitive binding assay suggest that there are at least three epitopes on a TMP molecule of the HIV-2[GH-1] isolate. The MAbs did not inhibit syncytium formation between HIV-2[GH-1]-infected MOLT-4 cells and MOLT-4 clone 8 cells, nor virus infection to MOLT-4 clone 8 cells.
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PMID:Production and characterization of mouse monoclonal antibodies against the transmembrane protein of a human immunodeficiency virus type 2. 172 59

Genetic variability in human immunodeficiency virus type 1 (HIV-1) has been studied extensively, but the total nucleotide sequence of the HIV-2 genome has been reported only in two strains. For phylogenetic analyses of HIV, the genetic variability of HIV-2 should be investigated. This paper reports the complete nucleotide sequence of an HIV-2 isolate from Ghana, HIV-2[GH-1]. This virus showed approximately 85% homology in overall nucleotide sequence with HIV-2ROD. The amino acid sequence of the gag and pol proteins of HIV-2[GH-1] showed 90% homology with those of HIV-2ROD, but its env gene and central regions were highly variable (more than 20% divergence in amino acids), indicating the presence of extensive genetic heterogeneity in HIV-2. However, the sequences with specific functions were relatively well conserved in these HIV-2 isolates.
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PMID:Genomic divergence of HIV-2 from Ghana. 261 Oct 42

We tested whether human immunodeficiency virus type 1 (HIV-1) could be differentiated from HIV-2 by a reverse transcriptase (RT)-typing assay that measured the reduction of enzyme activity owing to specific antibody. RT-inhibiting antibody was examined for HIV type specificity by a new nonradioisotopic RT assay. Antibodies from four rabbits immunized with recombinant HIV-1 RT and from 23 HIV-1-seropositive individuals all specifically inhibited the enzyme activities of two HIV-1 strains (LAV-1 and GH-3), three zidovudine-resistant HIV-1 mutants, and a recombinant HIV-1 RT. However, none of these antisera affected the activities of six HIV-2 strains (GH-1, GH-2, GH-4, GH-5, GH-6, LAV-2ROD), Rous-associated virus type 2, and DNA polymerase I from Escherichia coli. In contrast, HIV-2 antibody from a rabbit immunized with disrupted GH-1 virions blocked the enzyme activities of the six HIV-2 strains but not those of the three HIV-1 strains, Rous-associated virus type 2, or DNA polymerase I. These results indicate that the antigenic domains of HIV-1 and HIV-2 RTs recognized by their inhibiting antibodies are distinct from each other and are highly conserved. Clinical HIV isolates from 18 HIV-1-seropositive individuals and 3 HIV-2-seropositive Ghanaian individuals were identified as HIV-1 and HIV-2, respectively, by the nonradioisotopic RT-typing assay.
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PMID:Differentiation between human immunodeficiency virus type 1 (HIV-1) and HIV-2 isolates by nonradioisotopic reverse transcriptase-typing assay. 752 25

Antibodies inhibiting the reverse transcriptase (RT) of human immunodeficiency virus type-1 (HIV-1) were found to be generated in the serum of mice repeatedly infected with a vaccinia virus recombinant, WRRT, expressing the enzyme. A monoclonal antibody (mAb), 7C4, which specifically and almost completely inhibits the RNA-dependent DNA polymerase activity of HIV-1 RT was produced from a mouse repeatedly immunized with WRRT. 7C4 seems to be specific for HIV-1 among retroviruses: 7C4 inhibited RT activity of three strains of HIV-1 (IIIB, Bru, and IMS-1) but not of two strains of HIV-2 (GH-1 and LAV-2) or two strains of SIV (MAC and MND). The immunoglobulin isotype of three out of four mAbs produced from spleen cells of the immunized mouse were IgG2a. This immunization method that avoids protein denaturation may preferentially induce a T helper type-1 immune response and increase the chances of producing the only occasionally obtainable mAb capable of recognizing a conformational epitope and completely inhibiting enzyme activity.
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PMID:Generation of neutralizing antibody to the reverse transcriptase of human immunodeficiency virus type 1 by immunizing of mice with an infectious vaccinia virus recombinant. 932 86

More than 10 G protein-coupled receptors (GPCRs) have been reported to act as coreceptors for entry of human and simian immunodeficiency viruses (HIV and SIV). We investigated the utilization of six GPCRs as coreceptors by T-cell-line-adapted HIV-2 strains (CBL-20, CBL-21, CBL-23, GH-1, ROD, and SBL6669) and SIV strains (SIVagmTYO-1, SIVmac251, and SIVmndGB-1). NP-2/CD4 cells were transduced with CCR3, CCR5, CCR8, CXCR4, GPR1, or APJ, and examined for susceptibilities to cell-free HIV/SIV. HIV-2 strains were grouped into two types by their coreceptor usage. The first group, CBL-20 and CBL-21, used CXCR4 exclusively; the other four strains used a few or all of the six coreceptors. These strains could further infect CD4-negative NP-2/CXCR4 or NP-2/CCR5 cells in the presence (all strains) or absence (SBL6669 and ROD strains) of soluble CD4. SIVagm and SIVmnd infected NP-2/CD4/GPR1 cells. The coreceptors CCR3, CCR8, GPR1, and APJ did not mediate the CD4-independent infection. Although HIV-2ROD and SIVmnd infected both NP-2/CD4/CXCR4 and NP-2/CD4/CCR5 cells, only CXCR4 and CCR5, respectively, were used in CD4-independent infection. Binding of virions to CD4-negative cells occurred at 4 degrees C. These findings suggest that there may be a correlation between the promiscuous use of coreceptors by HIV-2/SIV strains and their ability to infect CD4-negative cells.
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PMID:CD4-Dependent and CD4-independent utilization of coreceptors by human immunodeficiency viruses type 2 and simian immunodeficiency viruses. 1111 2

Certain histocompatibility leukocyte antigen (HLA) alleles are associated with improved clinical outcomes for individuals infected with human immunodeficiency virus type 1 (HIV-1), but the mechanisms for their effects remain undefined. An early CD8(+) T-cell escape mutation in the dominant HLA-B57-restricted Gag epitope TW10 (TSTLQEQIGW) has been shown to impair HIV-1 replication capacity in vitro. We demonstrate here that this T(242)N substitution in the capsid protein is associated with upstream mutations at residues H(219), I(223), and M(228) in the cyclophilin A (CypA)-binding loop in B57(+) individuals with progressive disease. In an independent cohort of epidemiologically linked transmission pairs, the presence of these substitutions in viruses encoding T(242)N was associated with significantly higher plasma viremia in donors, further suggesting that these secondary mutations compensated for the replication defect of T(242)N. Using NL4-3 constructs, we illustrate the ability of these CypA loop changes to partially restore replication of the T(242)N variant in vitro. Notably, these mutations also enhanced viral resistance to the drug cyclosporine A, indicating a reduced dependence of the compensated virus on CypA that is normally essential for optimal infectivity. Therefore, mutations in TW10 allow HIV-1 to evade a dominant early CD8(+) T-cell response, but the benefits of escape are offset by a defect in capsid function. These data suggest that TW10 escape variants undergo a postentry block that is partially overcome by changes in the CypA-binding loop and identify a mechanism for an HIV-1 fitness defect that may contribute to the slower disease progression associated with HLA-B57.
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PMID:Escape and compensation from early HLA-B57-mediated cytotoxic T-lymphocyte pressure on human immunodeficiency virus type 1 Gag alter capsid interactions with cyclophilin A. 1772 32