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

An African lioness from the Zoo of Zurich had to be euthanized because of an inoperable tumor. The serum tested negative for feline leukemia virus (FeLV) p27 antigen by enzyme-linked immunosorbent assay (ELISA) but was strongly positive for feline immunodeficiency virus (FIV) antibodies by ELISA and Western blot. When her only offspring and mate were tested for FIV, high antibody titers to FIV were also found in their serum. Lymphocytes were prepared from these two lions on different occasions and co-cultivated with specific pathogen free (SPF) cat lymphocytes in the presence of concanavalin A and recombinant human interleukin-2 (IL-2) for 6 weeks. The cell culture supernatants tested negative for Mg(2+)-dependent reverse transcriptase and FIV p24 by a double antibody sandwich ELISA throughout the culture period. Whole blood and buffy coat cells collected from these two lions were transmitted by intraperitoneal injection into two SPF cats. The two cats did not seroconvert for a period of 11 months nor could reverse transcriptase activity and FIV p24 antigen be demonstrated in the supernatant of several lymphocyte cultures. To determine the importance of lentivirus infections in zoo-kept wild felids, 124 serum samples were obtained from African lions, Indian and Siberian tigers, snow leopards, panthers, cheetahs and other wild cats from nine European zoos. In addition, serum samples collected from 12 Asiatic lions originating from Gir forest in the Indian State of Gujarat were included in this study. The sera were tested for antibodies to FIV, FeLV and feline syncytium-forming virus (FeSFV) by ELISA and Western blot using the respective viruses after gradient purification. In addition, some of the sera were also tested for antibodies to equine infectious anemia virus (EIAV) and Visna-Maedi virus (VMV). Antibodies to FIV were found in 30/53 (57%) of African lions, one of 18 tigers and one of four panthers. All other sera including those collected from the 12 Asiatic lions were negative for FIV antibodies. Some of the FIV positive lion sera had high antibody titers producing strong bands on Western blot strips even in dilutions of >> 1:1000. The Western blot pattern of the lion sera differed from that of domestic cats in that primarily p24 and to a lesser degree p17 was recognized. Antibodies to FeSFV were found in 14 animals (seven with strong, seven with intermediate, reaction). No correlation was found between FIV and FeSFV infection. Antibodies to FeLV were found in two cheetahs which later turned out to have been vaccinated with Leukocell, a FeLV vaccine.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Retrovirus infections in non-domestic felids: serological studies and attempts to isolate a lentivirus. 133 98

The early stages of lentivirus infection of dendritic cells have been studied in an in vivo model. Maedi-visna virus (MVV) is a natural pathogen of sheep with a tropism for macrophages, but the infection of dendritic cells has not been proven, largely because of the difficulties of definitively distinguishing the two cell types. Afferent lymphatic dendritic cells from sheep have been phenotypically characterized and separated from macrophages. Dendritic cells purified from experimentally infected sheep have been demonstrated not only to carry infectious MVV but also to be hosts of the virus themselves. The results of the in vivo infection experiments are supported by infections of purified afferent lymph dendritic cells in vitro, in which late reverse transcriptase products are demonstrated by PCR. The significance of the infection of afferent lymph dendritic cells is discussed in relation to the initial spread of lentivirus infection and the requirement for CD4 T cells.
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PMID:Infection of dendritic cells by the Maedi-Visna lentivirus. 1102 38

Maedi-visna is a slow virus infection of sheep leading to a progressing lymphoproliferative disease which is invariably fatal. It affects multiple organs, but primarily the lungs where it causes interstitial pneumonia (maedi). Infection of the central nervous system was commonly observed in Icelandic sheep (visna), infection of mammary glands (hard udder) in sheep in Europe and the USA, and infection of the joints in sheep in the USA. The name ovine progressive pneumonia (OPP) is commonly used in the USA and ovine lentivirus (OvLV) infection is also a name used for maedi-visna. A related infection of goats, caprine arthritis-encephalitis (CAE), is common in Europe and the USA. The natural transmission of maedi-visna is mostly by the respiratory route, but also to newborn lambs by colostrum and milk. Intrauterine transmission seems to be rare and venereal transmission is not well documented. Macrophages are the major target cells of maedi-visna virus (MVV), but viral replication is greatly restricted in the animal host, apparently due to a posttranscriptional block. The low-grade viral production in infected tissues can explain the slow course of the disease in sheep. The lesions in maedi-visna consist of infiltrates of lymphocytes, plasma cells, and macrophages, and are detectable shortly after experimental transmission. Several studies indicate that the lesions are immune mediated and that cytotoxic T-lymphocytes may be important effector cells. The persistence of the MVV infection is explained by a reservoir of latently infected blood and bone marrow monocytes, which migrate into the target organs and mature into macrophages with proviral DNA transcription, but limited replication of virus. The MVV particles are morphologically similar to those of other retroviruses and the mode of replication follows the same general pattern. The genome organization and gene regulation resembles that of other lentiviruses. In addition to gag, pol and env, MVV has three auxiliary genes (tat, rev and vif), which seem to have similar functions as in other lentiviruses, with a possible exception of the tat gene. A determination of the 9200 nucleotide sequence of the MVV genome shows a close relationship to CAE virus, but limited sequence homology with other lentiviruses, and only in certain conserved domains of the reverse transcriptase and possibly in the surface protein. MVV infection in sheep and HIV-1 infection in humans have a number of features in common such as a long preclinical period following transmission, and a slow development of multiorgan disease with fatal outcome. A brief early acute phase, which is terminated by the immune response, is also an interesting common feature. Like HIV-1, MVV is macrophage tropic and the early stages of the HIV-1 infection which affect the central nervous system and the lungs are in many ways comparable to maedi-visna. In contrast to HIV-1, MVV does not infect T-lymphocytes and does not cause T-cell depletion and immunodeficiency. This is responsible for the difference in the late stages of the HIV-1 and MVV infections and the final clinical outcome. Despite limited sequence homology, certain proteins of MVV and HIV-1 show structural and functional similarities. Studies of MVV may therefore help in the search for new drugs against lentiviruses, including HIV-1.
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PMID:Maedi-visna virus and its relationship to human immunodeficiency virus. 1642 63

In small ruminant lentivirus infections, cellular immune responses are diminished in clinically affected animals. The underlying mechanisms for this are unknown. In this study, we tested the hypothesis that alterations in expression of the co-stimulatory molecules B7-1 and B7-2 are involved in infections with Visna/Maedi virus (VMV), the prototype lentivirus of sheep. We studied B7 expression levels ex vivo in peripheral blood mononuclear cells (PBMCs), determining B7 RNA levels by real time reverse transcriptase polymerase chain reaction in asymptomatic as well as clinically affected VMV-seropositive sheep. The levels of both B7 molecules were increased in VMV-seropositive asymptomatic sheep. However, in VMV clinically affected sheep, the level of CD80 (but not CD86) was low compared with the level in uninfected sheep (p < 0.05). CD80 and CD86 RNA levels were associated with the ability of PBMCs to respond to VMV gag antigens (p14, p17, and p25) by proliferation, with most seropositive asymptomatic sheep showing positive proliferative responses but clinically affected sheep showing no response. The response to p25 in clinically affected animals was increased by the addition of interleukin-2 to the cultures. Decreased recall responses to unrelated antigens (assessed by production of interferon-gamma) were also found in clinically affected sheep. Thus, among seropositive sheep, decreased B7-1 (CD80) RNA levels and diminished antigen-specific cellular immune responses in PBMCs point to a VMV disease status, whereas increased CD80 and CD86 levels and augmented cellular responses are linked to asymptomatic infection.
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PMID:Association of CD80 and CD86 expression levels with disease status of Visna/Maedi virus infected sheep. 1815 34

Maedi and visna are contagious sheep diseases which were introduced into Iceland in 1933 by imported sheep of Karakul breed. Maedi, a slowly progressing pneumonia, and the central nervous system disease visna were shown to be transmissible in sheep and most likely caused by a virus. In 1957, visna virus was isolated in tissue culture from sheep brain and maedi virus was isolated the following year from sheep lungs. Both viruses showed similar cytopathic effect in tissue culture. Electron microscope studies of ultrathin sections from visna virus infected cells demonstrated spherical particles, 70-100 nm in diameter, which were formed by budding from the cell membrane. Later studies showed identical particles in maedi virus infected cultures. These, and several other comparative studies, strongly indicated that maedi and visna were caused by strains of the same virus, later named maedi-visna virus (MVV). Comparative studies in tissue culture suggested that MVV was related to RNA tumor viruses of animals, the oncornaviruses. This was later supported by the finding that MVV is an RNA virus. A few months after reverse transcriptase was demonstrated in oncornaviruses, the enzyme was also found in MVV virions. Thus, MVV was classified as a retrovirus together with the oncornaviruses. However, MVV is not oncogenic in vivo or in vitro and was in 1975 placed in a subgroup of retroviruses named lentiviruses, which cause cytopathic effect in vitro and slowly progressing inflammatory disease in animals, but are nononcogenic. In the early 1980s, the causative agent of AIDS was found to be a non-oncogenic retrovirus and was classified as a lentivirus. Thus, HIV became the first human lentivirus.
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PMID:The origin of lentivirus research: Maedi-visna virus. 2327 53