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

To investigate the role of vpr (viral protein R) in the replication and cytopathicity of human immunodeficiency virus type 1 (HIV-1), infectious proviruses were constructed that were isogenic except for the ability to produce the protein product of vpr. The experiments described here demonstrate that vpr encodes a 96 amino acid 15 kDa protein. The vpr product increases the rate of replication and accelerates the cytopathic effect of the virus in T cells. Vpr acts in trans to increase levels of viral protein expression. The stimulatory effect of vpr is observed to act on the HIV-1 LTR as well as on several heterologous promoters.
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PMID:Identification of HIV-1 vpr product and function. 213 7

In transient gene expression assays we observed an increase in expression of the bacterial chloramphenicol acetyl-transferase (CAT) gene, under the transcriptional control of the HIV-1 LTR (pLTR-CAT), when this plasmid was cotransfected into Vero or MRC-5 cells with a plasmid containing either the HCMV immediate early 1 and 2 (E1, IE2) genes (pRL43a) or just the IE2 gene (pMP18). When the HCMV IE1 gene (pMP12) was cotransfected with pLTR-CAT into Vero cells the level of measurable CAT gene activity was below the level observed when pLTR-CAT was cotransfected with a nonspecific carrier plasmid (pGEM3). The negative influence of the HCMV IE1 gene product on the HIV-1 LTR in Vero cells was also observed when the HIV-1 tat gene (pLTR-TAT) was contransfected into Vero cells with pLTR-CAT and pMP12. However, when the HCMV IE1 gene was cotransfected into rhabdomyosarcoma (RD) cells with proviral HIV-1 DNA, an increase in viral production, as monitored by measurement of HIV-1 reverse transcriptase activity, was observed. In electrophoretic mobility shift assays, nuclear extracts obtained 15 hr post-HCMV infection (hpi) were found to contain a lower level of interaction with an oligonucleotide which corresponded to the HIV-1 LTR Sp-1 binding motif. Nuclear extracts obtained 40 hpi of MRC-5 cells had a greater level of interaction with, and changed the mobility of, the Sp-1 oligonucleotide relative to the uninfected nuclear extracts. HCMV-infected MRC-5 cell nuclear extracts also contain a factor(s) which interacted with the HIV-1 LTR between nucleotide positions -15 to -2 relative to the HIV-1 mRNA start site.
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PMID:Characterization of multiple molecular interactions between human cytomegalovirus (HCMV) and human immunodeficiency virus type 1 (HIV-1). 215

Increased concentrations of excitotoxin quinolinic acid in cerebrospinal fluid (CSF) are associated with infection with the human immunodeficiency virus (HIV-1) and have been implicated in the pathogenesis of the acquired immune deficiency syndrome (AIDS) dementia complex. In the present study, inoculation of macaques with D/1/California, an immunosuppressive serotype 1 type D retrovirus, was associated with acute and chronic increases in CSF and serum quinolinic acid concentrations in macaques that had developed SAIDS, a simian disease analogous to AIDS in humans--particularly macaques with demonstrable opportunistic infections. Kynurenic acid, an antagonist of excitatory amino acid receptors as well as the excitotoxic effects of quinolinic acid, was also increased in the CSF of SAIDS macaques, but to a significantly lesser degree than was quinolinic acid (kynurenic acid, 1.8-fold; quinolinic acid, 15.6-fold). CSF quinolinic acid, but not kynurenic acid, was also increased in viremic macaques with SAIDS-related complex (2.4-fold) and asymptomatic virus positive carriers (3.4-fold). Macaques that had recovered from D/1/California infection and were antibody positive and virus negative had normal CSF quinolinic acid and kynurenic acid concentrations. Increased activity of indoleamine-2,3-dioxygenase, the first enzyme of the kynurenine pathway, was indicated in the macaques with SAIDS by reduced serum L-tryptophan and elevated serum L-kynurenine concentrations. Macaques infected with D/1/California may provide a primate model for investigation of the mechanisms involved in increases in CSF quinolinic acid in retrovirus and other infectious diseases, including HIV-1. It remains to be determined whether the increased CSF quinolinic acid concentrations and the increased ratio of quinolinic acid to kynurenic acid have neurological significance or are a useful "marker" of infection.
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PMID:Increased ratio of quinolinic acid to kynurenic acid in cerebrospinal fluid of D retrovirus-infected rhesus macaques: relationship to clinical and viral status. 216 38

DNA integration appears to be an obligatory step for the efficient replication of retroviruses. Studies of the integration reaction for the avian and murine C-type retroviruses have defined the importance of: i) LTR terminal sequences, which are joined to host DNA, and ii) the activity of the retroviral integration protein (IN). The specific requirements for the integration of HIV DNA have not yet been defined. In this review, we survey studies pertinent to this reaction for HIV and extrapolate a mechanism for HIV DNA integration based upon knowledge of the integrative recombination reaction of the C-type retroviruses.
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PMID:HIV DNA integration: observations and interferences. 216 82

We investigated serum neopterin, tryptophan, and kynurenine concentrations in 23 HIV-1 seropositive patients (Walter Reed Stage 4-6). Ten patients presented with polyneuropathy and three with dementia, one of the patients with dementia also had polyneuropathy and dementia. We found significant associations between lower trytophan concentrations and neurologic/psychiatric symptoms. The negative correlation of tryptophan with kynurenine and neopterin concentrations indicates activity of indoleamine 2,3-dioxygenase (IDO) in patients. IDO can be induced by cytokines such as interferon-gamma and therefore low tryptophan levels may result from chronic immune stimulation in HIV-1 seropositives.
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PMID:Decreased serum tryptophan in patients with HIV-1 infection correlates with increased serum neopterin and with neurologic/psychiatric symptoms. 216 83

We have used a specific phosphatase inhibitor, okadaic acid, to examine the role of two phosphatases, PP1 and PP2A, in the induction of NF-kappa B and the long terminal repeat of the human immunodeficiency virus type 1 (HIV-LTR). Treatment of Jurkat cells with okadaic acid induced NF-kappa B in nuclear extracts. The rate of induction by okadaic acid was delayed compared to the induction of NF-kappa B by phorbol myristate acetate (PMA). The induction of NF-kappa B by okadaic acid was enhanced by cycloheximide or phytohemagglutinin (PHA). In contrast to PMA, okadaic acid appeared to induce NF-kappa B independently of protein kinase C (PKC). That the NF-kappa B induced by okadaic acid was functional was demonstrated by the marked increase in CAT activity that occurred in Jurkat, BJA-B, and U251 cells that were transfected with HIV-LTR-CAT and treated with okadaic acid. The increase in CAT activity triggered by okadaic acid was dependent on the presence of the NF-kappa B sites in the long terminal repeat of HIV as assessed by deletion and mutation analysis. Similarly to its effect on the induction of NF-kappa B, PHA added together with okadaic acid resulted in a further increase in CAT activity. Somewhat surprisingly, the addition of PMA inhibited the increase in CAT activity in response to okadaic acid, which suggests that the activation of PKC may also induce inhibitory factors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of nuclear factor-kappa B and the human immunodeficiency virus long terminal repeat by okadaic acid, a specific inhibitor of phosphatases 1 and 2A. 217 54

The tat gene of HIV is a strong activator of the viral LTR. The Tat protein contains a highly basic domain that is important for its transport to the nuclear/nucleolar locations. The Tat basic domain when fused to Escherichia coli beta-galactosidase directed the chimeric protein to the nucleus and nucleolus. Tat mutants lacking the entire basic domain were severely defective in trans-activation. Substitution of the basic domain of Tat with that of the functionally unrelated HIV-1 Rev protein targeted the chimeric protein to the nucleolus and restored the function of Tat. In contrast, substitution with the nuclear targeting signal (NLS) of SV40 T antigen targeted the chimeric protein to the nucleus and accumulation in the nucleolar region was excluded. The Tat-NLS chimeric protein did not restore the trans-activation function of Tat efficiently. These results indicate that the arginine-rich basic domain of the trans-activator, Tat, and post-transcriptional trans-regulator, Rev, are functionally similar with regard to trans-activation of HIV-1 LTR.
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PMID:Functional substitution of the basic domain of the HIV-1 trans-activator, Tat, with the basic domain of the functionally heterologous Rev. 218 74

Replication of HIV-1 requires Tat, which stimulates gene expression through a target sequence, TAR. It is known that TAR is a Tat-responsive target. Since Tat increases transcriptional initiations from the HIV-1 LTR promoter, it is unclear mechanistically how Tat utilizes an RNA target. Here we show that TAR RNA is only one component of the Tat-responsive target. Efficient Tat trans-activation was observed only when TAR was present in conjunction with the HIV-1 LTR NF-kappa B/SP1 DNA sequences. TAR RNA outside of this context produced a suboptimal Tat response. We propose that TAR RNA serves an attachment function directing Tat to the LTR. A Tat protein engineered to interact with LTR DNA could trans-activate through a TAR-independent mechanism. This suggests that Tat also has a DNA target.
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PMID:TAR-independent activation of the HIV-1 LTR: evidence that tat requires specific regions of the promoter. 220 51

To study the functional mechanism of the hepatitis B virus (HBV) X (hbx) gene product, we have expressed the hbx protein in E. coli and purified it by HPLC. The purified hbx protein was shown to be active in transactivating transcription directed by the LTR sequence of HIV-1. The hbx protein was found to have an intrinsic serine/threonine protein kinase activity. The hbx protein was detected in hepatitis B virions, and tryptic phosphopeptide maps of the hbx protein phosphorylated in the virion and of the in vitro phosphorylated bacterially expressed hbx protein were similar. Inactivation of the hbx protein by heat, protein-denaturing agents, or an ATP affinity analog, p-fluorosulfonylbenzoyl 5'-adenosine, resulted in loss of both protein kinase activity and trans-activation activity. These results suggest that the HBV-encoded trans-activator hbx is a novel protein kinase.
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PMID:The hepatitis B virus-encoded transcriptional trans-activator hbx appears to be a novel protein serine/threonine kinase. 222 72

Studies of NF-kappa B suggest that this enhancer binding activity corresponds to a family of at least four proteins (p50, p55, p75, and p85) differentially induced with biphasic kinetics during T cell activation. While p55 and p50 are closely related to the 50 kd DNA binding subunit of NF-kappa B, p75 and p85 exhibit DNA binding properties that distinguish them from this 50 kd polypeptide and its regulatory subunits I kappa B and p65. All four members of this kappa B-specific protein family are structurally related to the v-Rel oncoprotein and one, p85, appears identical to human c-Rel. v-Rel, but not nontransforming v-Rel mutants, binds to the kappa B enhancer and inhibits NF-kappa B-activated transcription from the IL-2 receptor alpha promoter and HIV-1 LTR. These findings suggest a Rel-related family of kappa B enhancer binding proteins and raise the possibility that the transforming activity of v-Rel is linked to its inhibitory action on cellular genes under NF-kappa B control.
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PMID:The v-rel oncogene encodes a kappa B enhancer binding protein that inhibits NF-kappa B function. 222 78


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