Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Feline immunodeficiency virus (FIV) has morphological, physical and biochemical characteristics similar to human immunodeficiency virus (HIV), the cause of AIDS in man. However, it is antigenically and genetically distinct from HIV; an antigenic relatedness with equine infectious anaemia virus has been demonstrated. FIV has been molecularly cloned and sequenced. Diagnostic tests are commercially available and attempts at preparing inactivated, subunit and molecularly engineered vaccines are being made in different laboratories. During FIV infection a transient primary illness can be recognized, with fever, neutropenia and lymphadenopathy. After a long period of clinical normalcy a secondary stage is distinguished with signs of an immunodeficiency-like syndrome. The incubation period for this stage can be as long as 5 years, during which gradual impairment of immune function develops. Many FIV-infected cats are presented for the first time showing vague signs of illness: recurrent fevers, emaciation, lack of appetite, lymphadenopathy, anaemia, leucopenia and behavioural changes. Later, the predominant clinical signs observed are chronic stomatitis/gingivitis, enteritis, upper respiratory tract infections, and infections of the skin. Neoplasias, neurological, immunological and haematological disorder are seen in a smaller proportion. The immunodeficiency-like syndrome is progressive over a period of months to years. Concomitant infection with feline leukaemia virus has been shown to accelerate the progression of disease. In vitro, phenotypic mixing between FIV and an endogenous feline oncovirus (RD114) has been demonstrated which leads to a broadening of the cell spectrum of the lentivirus. Bovine immunodeficiency virus (BIV) has been isolated only once, and all attempts to obtain additional isolates have failed; it has been recovered from the leucocytes of cattle with persistent lymphocytosis, lymphadenopathy, lesions in the central nervous system, progressive weakness and emaciation. As with the feline representative, BIV also was found to possess a lentivirus morphology and to encode a reverse transcriptase with Mg++ preference; it replicates and induces syncytia in a variety of embryonic bovine tissues in vitro. Antigenic analyses have demonstrated a conservation of epitopes between the major core protein of BIV and HIV. The original isolate has been molecularly cloned and sequenced. Besides the three large open reading frames (ORFs) comprising the gag, pol, and env genes common to all replication-competent retroviruses, five additional small ORFs were found. Numerous point mutations and deletions were found, mostly in the env-encoding ORF. These data suggest that, within a single virus isolate, BIV displays extensive genomic variation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Animal immunodeficiency viruses. 133 43

TED is a lepidopteran retrotransposon found inserted within the DNA genome of the Autographa californica nuclear polyhedrosis virus mutant, FP-D. To examine the proteins and functions encoded by this representative of the gypsy family of retrotransposons, the gag- and pol-like open reading frames (ORFs 1 and 2) were expressed in homologous lepidopteran cells by using recombinant baculovirus vectors. Expression of ORF 1 resulted in synthesis of an abundant TED-specific protein (Pr55gag) that assembled into viruslike particles with a diameter of 55 to 60 nm. Expression of ORF 2, requiring a -1 translational frameshift, resulted in synthesis of a protease that mediated cleavage of Pr55gag to generate p37, the major protein component of the resulting particles. Expression of ORF 2 also produced reverse transcriptase that associated with these particles. Both protease and reverse transcriptase activities mapped to domains within ORF 2 that contain sequence similarities with the corresponding functional domains of the pol gene of the vertebrate retroviruses. These results indicated that TED ORFs 1 and 2 functionally resemble the retrovirus gag and pol genes and demonstrated for the first time that an invertebrate member of the gypsy family of elements encodes active forms of the structural and enzymatic functions necessary for transposition via an RNA intermediate. TED integration within the baculovirus genome thus represents one of the first examples of transposon-mediated transfer of host-derived genes to an eukaryotic virus.
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PMID:The baculovirus-integrated retrotransposon TED encodes gag and pol proteins that assemble into viruslike particles with reverse transcriptase. 137 Nov 68

A cell line (BsT) established from neoplastic embryonal tissues of the platyfish (Xiphophorus maculatus) released spontaneously retrovirus-like particles. The particles have a buoyant density of 1.16 g/ml, a mean diameter of 100 nm and the morphology of immature retroviruses. The particle-associated proteins p70, p65, and p28 react with an antiserum directed against the major internal feline leukemia virus structural protein p27. The particles are associated with a reverse transcriptase. The purified enzyme has a molecular weight of about 70 kDa and prefers the template primers poly(rA):oligo(dT), poly(dC):oligo(dG), and poly(rC):oligo(dG) in the presence of Mn2+. The enzyme activity is inhibited by antibodies directed against the reverse transcriptase of feline leukemia virus and simian sarcoma virus. The particles contain a ribonucleic acid of about 70 S. In an endogenous reverse transcriptase reaction nucleic acids in the range of 0.2 to 0.4 kb were synthesized. In Northern blots with these nucleic acids as probe, three transcripts of about 8.5, 4.2, and 1.5 kb were detected in BsT cells. Southern blot analysis with the same probe demonstrates related sequences in the DNA of BsT cells and the platyfish and swordtail (Xiphophorus helleri). Hybridization experiments with the LTR-gag region of the feline leukemia virus show homologous sequences in the Xiphophorus genome.
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PMID:Isolation and characterization of a retrovirus from the fish genus Xiphophorus. 137 84

A retrotransposon from the fungal tomato pathogen Cladosporium fulvum (syn. Fulvia fulva) has been isolated and characterised. It is 6968 bp in length and bounded by identical long terminal repeats of 427 bp; 5 bp target-site duplications were found. Putative first- and second-strand primer binding sites were identified. Three long open reading frames (ORFs) are predicted from the sequence. The first has homology to retroviral gag genes. The second includes sequences homologous to protease, reverse transcriptase, RNAse H and integrase, in that order. Sequence comparisons of the predicted ORFs indicate that this element is closely related to the gypsy class of LTR retrotransposons. Races of the pathogen exhibit polymorphisms in their complement of at least 25 copies of the sequence. Virus-like particles which co-sediment with reverse transcriptase activity were observed in homogenates of the fungus. This is the first report of an LTR retrotransposon in a filamentous fungus.
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PMID:CfT-I: an LTR-retrotransposon in Cladosporium fulvum, a fungal pathogen of tomato. 137 73

AIDS dementia complex is a common neurologic disorder in later stages of HIV-1 infection. Because virus-specific CTL have been shown to contribute to neurologic disease in certain viral illnesses, we examined the cerebrospinal fluid of HIV-1-infected persons with various stages of AIDS dementia complex for the presence of HIV-1-specific CTL. In five of six subjects studied, HIV-1-specific CTL were identified in the cerebrospinal fluid. These CTL were directed at epitopes within the gag, reverse transcriptase, envelope, and nef proteins and restricted by HLA class I Ag. In four of these subjects, virus-specific CTL were detected in higher numbers in the cerebrospinal fluid compared to the peripheral blood, suggesting a specific recruitment to or local induction within the nervous system. These studies demonstrate the presence of a vigorous and broadly directed CTL response to HIV-1 in the central nervous system of infected persons with AIDS dementia complex, and provide immunologic evidence of localized intrathecal infection. Although HIV-1-specific CTL may serve to inhibit viral replication in the central nervous system, the presence of a persistent CTL response in the central nervous system may also contribute to the neurologic disorders characteristic of HIV-1 infection.
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PMID:Detection of a vigorous HIV-1-specific cytotoxic T lymphocyte response in cerebrospinal fluid from infected persons with AIDS dementia complex. 138 38

The expression of the pol gene of human immunodeficiency virus type 1 occurs via a ribosomal frameshift between the gag and pol genes. The resulting protein, a Gag-Pol polyprotein, is produced at a level 5 to 10% of that of the Gag protein. The Gag-Pol polyprotein is incorporated into virions and provides viral protease, reverse transcriptase, and integrase, which are essential for infectivity. It is generally believed that the Gag-Pol polyprotein is incorporated into virions via interaction with the Gag protein, although the details of the mechanism are unknown. To further study this problem, we have constructed a human immunodeficiency virus type 1 proviral genome which overexpresses the Gag-Pol polyprotein (Pr160gag-pol). Transfection of this proviral genome (pGPpr-) into COS-1 cells resulted in the expression of full-length Pr160gag-pol polyprotein. Although the majority of the Pr160gag-pol was confined to the cells, low levels of reverse transcriptase activity were detectable in the cell supernatants. The cotransfection of pGPpr- with a second plasmid which expresses only the Pr55gag precursor (pGAG) resulted in a significantly higher level of Pr160gag-pol in the medium of transfected cells. Sedimentation analysis using sucrose density gradients demonstrated that most Pr160gag-pol was found in fractions corresponding to the density of virion particles, indicating that the Pr160gag-pol polyprotein was released in association with a Pr55gag viruslike particle. To further characterize the requirements for the release, a mutation was constructed to express an unmyristylated Pr160gag-pol polyprotein. Coexpression with Pr55gag demonstrated that the unmyristylated Pr160gag-pol was also incorporated into virion particles. Subcellular fractionation experiments revealed that the distributions of the Pr160gag-polmyr- and Pr160gag-pol in the membrane and cytosol were similar under low- or high-ionic-strength conditions. Taken together, these results suggest that myristylation of the Pr160gag-pol polyprotein is not required for the interaction with the Pr55gag necessary for packaging into a viruslike particle.
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PMID:The nonmyristylated Pr160gag-pol polyprotein of human immunodeficiency virus type 1 interacts with Pr55gag and is incorporated into viruslike particles. 138 61

Beside the risk of infection via HIV-1-contaminated blood, ophthalmologists are especially interested in the possibility of HIV-1 infection via tears. Therefore we tried to isolate HIV-1 from tears of 50 HIV-1-infected persons in different stages of disease by reverse transcriptase (RT) and by p24-antigen (p24-AG) in the cultures. Simultaneously we tried to isolate HIV-1 in the supernatant from peripheral blood lymphocytes (PBL), which was successful in 32 of the 50 examined specimens. HIV-1 could not be isolated from the tears of these persons. In addition, polymerasechain-reaction (PCR) was performed to detect proviral sequences (gag, pol, env) of HIV-1 in tears and blood of ten HIV-1-infected patients. While in all the examined patients gag, pol and env could be detected in the blood samples, only one tear sample was found positive for gag and pol DNA fragments. These results indicate that tears of HIV-1-positive contain extremely low quantities of tissue culture infectious doses (TCID) of HIV-1 in contrast to PBL. HIV-1 infection via tears therefore appears to be unlikely.
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PMID:Infrequent detection of HIV-1 components in tears compared to blood of HIV-1-infected persons. 138 31

Human immunodeficiency virus (HIV) has been implicated as the etiologic agent of acquired immunodeficiency syndrome and is a member of the sub-family Lentivirinae within the family Retroviridae. HIV type 1 (HIV-1) contains three major genes, gag, pol and env, which code for (1) core proteins, (2) a protease, reverse transcriptase and integrase, and (3) envelope glycoproteins, respectively. The core proteins p17, p24 and p15 are derived from gag precursor, p55, by endoproteolytic cleavage. The two nucleic-acid-binding proteins p7 and p9 are synthesized from p15 by proteolytic cleavage. These two structural proteins are apparently needed for the ribonucleoprotein-core formation. The envelope glycoproteins gp120 and gp41 (gp120-gp41 complex) are also generated by cleavage env precursors, gp160. The assembly of HIV-1 particles, like other retroviruses, appears to involve the association of the env precursor gp160 with the gag proteins. There are several factors which influence the assembly and budding process of HIV-1. In this article, we describe important events in HIV-1 morphogenesis and factors which influence this aspect of the HIV-1 life cycle.
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PMID:Morphogenesis of human immunodeficiency virus type 1. 138 14

HTLV-I is associated with a neurological syndrome designated Tropical Spastic Paraparesis/HTLV-I associated myelopathy (TSP/HAM). To determine whether HTLV-I can replicate in human primary macrophages and thus contribute to HTLV-I dissemination in the nervous system, elutriated human macrophages were infected cell-free with the HTLV-ICR and HTLV-IBOU isolates from patients with adult T-cell leukemia and TSP/HAM, respectively. Viral production was monitored by measuring the viral p24 gag antigen in the cell culture supernatant, by electron microscopy (EM) and by polymerase chain reaction (PCR) on viral DNA and RNA. The HTLV-I p24 gag antigen was detected 21 days after infection with either isolate, and the presence of mature viral particles was demonstrated by electron microscopy one month after infection. Viral sequences were amplified by PCR analysis of the infected macrophages' DNA. Spliced mRNAs for the p40tax and p27rex proteins, as well as the p12I, and p30II proteins encoded by the pX region were readily identified by reverse transcriptase PCR. Altogether, these data indicate that HTLV-I replication occurs in vitro in primary human macrophages. Whether macrophage infection occurs also in vivo and is a crucial step in the induction of the neurological manifestations observed in TSP/HAM remains an open question.
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PMID:In vitro infection of human macrophages by human T-cell leukemia/lymphotropic virus type I (HTLV-I). 148 73

The gag-pol coding region of the HIV-2BEN genome was expressed in CV-1 cells infected with four recombinant vaccinia viruses (VV). These recombinant VV encoded either the whole gag-pol region or the gag gene including the protease-coding region of the pol gene or the gag gene truncated at its 3'-end or only the pol gene. The HIV-2BEN gag precursor p55, its mature cleavage products p24 and p17 as well as the pol reverse transcriptase (RT) p66 were detected in VV-infected CV-1 cells. The p55 and two intermediate cleavage products p40 and p35 were myristilated. Comparison to lysates of permanently HIV-2BEN-infected Molt 4 clone 8 cells revealed that several additional gag and pol proteins were present in the VV-infected CV-1 cells. Deletion of the gag and pol overlapping region coding for the viral protease prevented cleavage of the recombinant gag precursor. Electron microscopy of VV-infected CV-1 cells revealed budding structures and immature as well as mature retroviral particles formed by the recombinant gag proteins. Striking differences in the ability to form complete particles were observed between the different recombinant VV. Expression of the truncated gag gene led to the formation of budding structures, but completely budded circular particles were not detectable. Such particles were produced by expression of the whole gag gene and the protease. Mature virions with an internal core structure were only detected in VVgagpol-infected cells. From these findings we conclude that the 3'-end of the gag gene coding for the p16 protein is essential for the formation of complete HIV-2 particles and that the pol proteins support the assembly of the viral core.
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PMID:Morphogenesis of recombinant HIV-2 gag core particles. 152 43


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