Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

T22 ([Tyr5,12, Lys7]-polyphemusin II) is a strong anti-HIV compound. Six analogs of T22 and two natural forms were synthesized. Of them, all downsized peptides (14 residues; TW70, T131, T134, and T140) showed a higher selectivity index than did other, 17- or 18-residue peptides. In particular, T134 and T140 showed both lower cytotoxicity and higher antiviral activity than did T22 against HIV infection of MT-4 cells, an HTLV-I-bearing T cell line. To clarify the inhibitory mode of T22 and its analogs, we used a single-round replication assay (luciferase assay), in which different envelope-bearing pseudotypes were used to infect CXCR4- or CCR5-bearing U87 cells via CD4. All of the analogs inhibited T cell line-tropic strain HXB-2 (X4) and dual-tropic strain 89.6 (R5X4) HIV infections mediated by CXCR4, but had no effect on macrophage-tropic strain ADA (R5) or 89.6 HIV infections mediated by CCR5. The inhibition by T134 (IC50 of 2.70 nM) and T140 (IC50 of 0.432 nM) was also stronger than that by T22 (IC50 of 5.05 nM). The binding of anti-CXCR4 monoclonal antibody 12G5 to lymphoma-derived T cell line Sup-T1 was more efficiently blocked by T134 and T140 than by T22. Taken together, T22 and its analogs T134 and T140 exerted their inhibition by specific binding to CXCR4. The marked increase in the anti-HIV activity of T134 and T140 was ascribed to an enhancement in their ability to bind to CXCR4.
AIDS Res Hum Retroviruses 1999 Mar 20
PMID:Marked increase in anti-HIV activity, as well as inhibitory activity against HIV entry mediated by CXCR4, linked to enhancement of the binding ability of tachyplesin analogs to CXCR4. 1019 51

Human herpesvirus 6 (HHV-6) has been implicated as a cofactor in the progressive loss of CD4(+) T cells observed in AIDS patients. Because dendritic cells (DC) play an important role in the immunopathogenesis of human immunodeficiency virus (HIV) disease, we studied the infection of DC by HHV-6 and coinfection of DC by HHV-6 and HIV. Purified immature DC (derived from adherent peripheral blood mononuclear cells in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4) could be infected with HHV-6, as determined by PCR analyses, intracellular monoclonal antibody staining, and presence of virus in culture supernatants. However, HHV-6-infected DC demonstrated neither cytopathic changes nor functional defects. Interestingly, HHV-6 markedly suppressed HIV replication and syncytium formation in coinfected DC cultures. This HHV-6-mediated anti-HIV effect was DC specific, occurred when HHV-6 was added either before or after HIV, and was not due to decreased surface expression or function of CD4, CXCR4, or CCR5. Conversely, HIV had no demonstrable effect on HHV-6 replication. These findings suggest that HHV-6 may protect DC from HIV-induced cytopathicity in AIDS patients. We also demonstrate that interactions between HIV and herpesviruses are complex and that the observable outcome of dual infection is dependent on the target cell type.
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PMID:Human herpesvirus 6 infects dendritic cells and suppresses human immunodeficiency virus type 1 replication in coinfected cultures. 1019 98

HIV-1 infection of nonhuman primates does not lead to the acquired immunodeficiency syndrome seen in humans. The basis for this lack of disease progression in these animals is still unknown. In this study, primary nonhuman primate peripheral blood mononuclear cells (PBMC) were tested for their susceptibility to in vitro infection by several different primary HIV-1 isolates representing distinct subtypes or clades. None of the five HIV-1 subtypes tested were able to readily establish an infection in chimpanzee or baboon PBMC, as determined by p24 antigen capture assays. To address the mechanism of in vitro resistance to HIV-1 infection, PBMC were analyzed for HIV coreceptor mRNA expression and cell surface expression. Flow cytometry analysis of the nonhuman primate PBMC demonstrated that they do express CD4, CCR3, CCR5, and CXCR4 on their cell surface. Therefore, the level of restriction in the virus replication cycle does not appear to lie at the point of entry in these cells.
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PMID:Analysis of nonhuman primate peripheral blood mononuclear cells for susceptibility to HIV-1 infection and HIV coreceptor expression. 1022 72

We have studied envelope protein from a donor with nonprogressive HIV-1 infection whose serum contains broadly cross-reactive, primary virus NA. DNA was extracted from lymphocytes, which had been collected approximately 6 and 12 months prior to the time of collection of the cross-reactive serum, and env genes were synthesized, cloned, expressed on pseudoviruses, and phenotyped in NA assays. Two clones from each time point had identical V3 region nucleotide sequences, utilized CCR5 but not CXCR4 for cell entry, and had similar reactivities with reference sera. Analysis of the full nucleotide sequence of one clone (R2) demonstrated it to be subtype B and have normal predicted glycosylation. R2 pseudovirus was compared with others expressing env genes of various clades for neutralization by sera from U.S. donors (presumed or known subtype B infections), and from individuals infected with subtypes A, C, D, E, and F viruses. Neutralization by the U.S. sera of R2 and other clade B pseudoviruses was low to moderate, although R2 was uniquely neutralized by all. R2 was neutralized by 3/3, 3/3, 2/5, 5/8, and 3/4 clade A, C, D, E, and F sera, respectively. R2 and a clade E pseudovirus were neutralized by largely complementary groups of sera, potentially defining two antigenic subgroups of HIV-1. The results suggest that the epitope(s) that induced the cross-clade reactive NA in donor 2 may be expressed on the R2 envelope.
AIDS Res Hum Retroviruses 1999 Apr 10
PMID:Expression and characterization of HIV type 1 envelope protein associated with a broadly reactive neutralizing antibody response. 1022 33

Three genes which have variants acting as anti-HIV-1 were described so far. Among three, two are genes encoding receptors for chemokines, namely CCR5 and CCR2, which act as entry coreceptors for HIV-1 virus. The other gene is SDF1 gene. SDF-1, a cytokine belonging to the chemokine family has an inhibitory activity against the HIV-1 infection, because SDF-1 Is the physiological ligand for CXCR4, the entry coreceptor for T tropic HIV-1 virus. Recently, an SDF1 gene polymorphism was figured out to be one of the human genetic factors which regulate the period between the HIV-1 infection and the AIDS onset. By this finding, it was strongly suggested that SDF-1 regulates the onset of AIDS in the actual human population.
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PMID:[Anti-HIV-1 genes; genetic restriction of AIDS pathogenesis by gene variants]. 1022 98

The frequencies of three mutations conferring resistance to HIV/AIDS were determined in a population sample of native Kuwaitis. The CCR2-641, SDF1-3'A, and CCR5-m303 mutations were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) tests using restriction endonucleases Bsa BI, Msp I, and Hinc II, respectively. The frequency of the mutant alleles were: for CCR2-641, 0.1195 (95% CI 0.0801-0.1694); for SDF1-3'A, 0.2593 (95% CI 0.2024-0.3231), and for CCR5-m303, less than 0.0025. Thus, the CCR2-641 and especially SDF1-3'A mutations are sufficiently common in Arabs and can be used for prognostic genotyping in HIV-infected individuals from the Gulf countries.
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PMID:Frequencies of SDF-1 chemokine, CCR-5, and CCR-2 chemokine receptor gene alleles conferring resistance to human immunodeficiency virus type 1 and AIDS in Kuwaitis. 1022 46

The National AIDS Control and Prevention Program of the Cambodian ministry of health has reported that the prevalence of HIV-1 infection among blood donors in Cambodia increased from less than 1% in 1991 to 4% in 1996, and that 39.3% of prostitutes, 7.1% of military personnel, 3.2% of pregnant women, and 5.2% of tuberculosis patients were infected in 1997. Findings are presented from an investigation of the genetic and biological features of HIV-1 strains in Cambodia. Viruses from 95 HIV-1-seropositive individuals were subtyped by heteroduplex mobility assay (HMA) and 23 were further analyzed for their biologic characteristics. 89 people were clearly infected with HIV-1 subtype E. The other 6 samples, however, were sequenced together with 17 HMA subtype E samples. All but 1 of these latter 23 Cambodian env sequences clustered with previously described Thai and Vietnamese subtype E sequences bearing a GPGQ motif at the tip of the V3 loop, with the last having a GPGR motif and being phylogenetically equidistant from Asian and African subtype E viruses. Nonsyncytium-inducing, CCR5-dependent viruses predominated in patients of clinical stage B, and were detected in about half of the stage C patients. All syncytium-inducing strains, mostly from AIDS patients, used both CCR5 and CXCR4. The presence of syncytium-inducing viruses did not correlate with the plasma viral load. These data show that CCR5-dependent HIV-1 subtype E currently predominates in Cambodia. The dynamics of the viral population during subtype E infection in Southeast Asia appear to be similar to that of subtype B infection in Europe and the US.
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PMID:Predominance of CCR5-dependent HIV-1 subtype E isolates in Cambodia. 1022 31

The hypervariable V3 loop within gp120 of human immunodeficiency virus type 1 (HIV-1) is the major determinant of cell tropism and the entry coreceptor usage of the virus. However, the information obtained thus far has been from only subtype B from North America and Europe, and little is known about other subtypes whose V3 amino acids differ by as much as 50% from subtype B V3. In this study, we examined the functional potential of the V3 element of the HIV-1 subtype E, the most crucial variant causing the AIDS epidemic throughout southeast Asia. A panel of HIV-1LAI recombinants was constructed by the overlap extension method, by which the LAI V3 loop was precisely replaced by that of the subtype E nonsyncytium-inducing (NSI) or syncytium-inducing (SI) variant. All of the recombinant viruses infected peripheral blood mononuclear cells, whereas only those with SI V3 infected MT2 cells, a CD4(+) T cell line. Consistently, the SI V3 recombinants used CXCR4, while the NSI V3 recombinants used CCR5 for infection of HOS-CD4(+) cells. Finally, only the NSI V3 sequence conferred CC-chemokine sensitivity on the parental virus. The data support the notion that the HIV-1 V3 loop consists of a relatively independent domain in gp120 and suggest that the subtype E V3 loop indeed contains the functional element to dictate the cell tropism, coreceptor preference, and chemokine sensitivity of the virus. These findings are of immediate importance in understanding V3 structure-function relationship and for examining phenotypic evolution of HIV-1 subtype E.
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PMID:Functional complementation of the envelope hypervariable V3 loop of human immunodeficiency virus type 1 subtype B by the subtype E V3 loop. 1032 59

It has been estimated that, to date, about 48% of all HIV-infected people in the world carry HIV-1 subtype C virus. Therefore, it is of great importance to gain better knowledge about the genetic and biological characteristics of this virus subtype. In the present study, the biological properties of HIV-1 isolates obtained from nine Ethiopian patients with AIDS were studied. DNA sequencing of the V3 loop of gp120 classified the isolates as subtype C. In primary isolation cultures, virus infection was accompanied by syncytium formation and cell lysis. Interestingly, when examining the growth in primary monocyte-macrophage cultures, initial low-level virus replication was followed by a nonproductive state, from which virus could be rescued by cocultivation with Jurkat(tat) cells. Furthermore, none of the isolates replicated in T cell lines (CEM, MT-2, HuT-78, and H9) or in the promonocytic cell line U937 clone 2. All isolates could use CCR5 as coreceptor, whereas no isolates could use CCR2b, CCR3, CCR5, CXCR4, Bonzo/STRL33, or BOB/GPR15. The genotype of the V3 region correlated with the MT-2 negative/non-syncytium-inducing (NSI) phenotype. Comparative studies revealed that the scarcity of CXCR4 usage as well as other phenotypic characteristics of subtype C isolates distinguish this subtype. On the basis of these data, we suggest that in addition, factors other than viral phenotype may govern the pathogenic potential of subtype C isolates.
AIDS Res Hum Retroviruses 1999 May 01
PMID:Phenotypic characteristics of human immunodeficiency virus type 1 subtype C isolates of Ethiopian AIDS patients. 1033 43

Chemokine receptors, particularly CCR5 and CXCR4, act as essential coreceptors in concert with CD4 for cellular entry by human immunodeficiency virus type 1 (HIV-1; reviewed in [1]). But infection of CD4(-) cells has also been encountered in various tissues in vivo, including astrocytes, neurons and microvascular endothelial cells of the brain [2] [3] [4] [5] [6], epithelial cells [5] [7], CD4(-) lymphocytes and thymocytes [8] [9], and cardiomyocytes [10]. Here, we present evidence for the infection of CD4(-) cell lines bearing coreceptors by well-known HIV-1 strains when co-cultured with CD4(+) cells. This process requires contact between the coreceptor-bearing and CD4(+) cells and supports the full viral replication cycle within the coreceptor-bearing target cell. Furthermore, CD4 provided in trans facilitates infection of primary human cells, such as brain-derived astrocytes. Although the pathobiological significance of infection of CD4(-) cells in vivo remains to be elucidated, this trans-receptor mechanism may facilitate generation of hidden reservoirs of latent virus that confound antiviral therapies and that contribute to specific AIDS-associated clinical syndromes.
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PMID:A trans-receptor mechanism for infection of CD4-negative cells by human immunodeficiency virus type 1. 1033 29


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