scholarly journals Integration Site Choice of a Feline Immunodeficiency Virus Vector

2006 ◽  
Vol 80 (17) ◽  
pp. 8820-8823 ◽  
Author(s):  
Yubin Kang ◽  
Christopher J. Moressi ◽  
Todd E. Scheetz ◽  
Litao Xie ◽  
Diane Thi Tran ◽  
...  
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Integration Site ◽  
Leukemia Virus ◽  
Foamy Virus ◽  
Moloney Murine Leukemia Virus ◽  
Human Hepatoma Cells ◽  
Immunodeficiency Virus ◽  
Integration Sites ◽  
Primate Lentiviruses ◽  
Transcriptional Units

ABSTRACT We mapped 226 unique integration sites in human hepatoma cells following gene transfer with a feline immunodeficiency virus (FIV)-based lentivirus vector. FIV integrated across the entire length of the transcriptional units. Microarray data indicated that FIV integration favored actively transcribed genes. Approximately 21% of FIV integrations within transcriptional units occurred in genes regulated by the LEDGF/p75 transcriptional coactivator. DNA in regions of FIV insertion sites exhibited a “bendable” structure and a pattern of duplex destabilization favoring strand separation. FIV integration preferences are more similar to those of primate lentiviruses and distinct from those of Moloney murine leukemia virus, avian sarcoma leukosis virus, and foamy virus.

scholarly journals Mouse Mammary Tumor Virus Integration Site Selection in Human and Mouse Genomes

2007 ◽  
Vol 82 (3) ◽  
pp. 1360-1367 ◽  
Author(s):  
Alexander Faschinger ◽  
Francoise Rouault ◽  
Johannes Sollner ◽  
Arno Lukas ◽  
Brian Salmons ◽  
...  
Keyword(s):  
Integration Site ◽  
Leukemia Virus ◽  
Transcription Start Sites ◽  
Mouse Mammary Tumor ◽  
Immunodeficiency Virus ◽  
Integration Sites ◽  
Tumor Virus ◽  
Mouse Cells ◽  
Human And Mouse ◽  
Integration Site Selection

ABSTRACT Based on integration site preferences, retroviruses can be placed into three groups. Viruses that comprise the first group, murine leukemia virus and foamy virus, integrate preferentially near transcription start sites. The second group, notably human immunodeficiency virus and simian immunodeficiency virus, preferentially targets transcription units. Avian sarcoma-leukosis virus (ASLV) and human T-cell leukemia virus (HTLV), forming the third group, show little preference for any genomic feature. We have previously shown that some human cells sustain mouse mammary tumor virus (MMTV) infection; therefore, we infected a susceptible human breast cell line, Hs578T, and, without introducing a species-specific bias, compared the MMTV integration profile to those of other retroviruses. Additionally, we infected a mouse cell line, NMuMG, and thus we could compare MMTV integration site selection in human and mouse cells. In total, we examined 468 unique MMTV integration sites. Irrespective of whether human or mouse cells were infected, no integration bias favoring transcription start sites was detected, a profile that is reminiscent of that of ASLV and HTLV. However, in contrast to ASLV and HTLV, not even a modest tendency in favor of integration within genes was observed. Similarly, repetitive sequences and genes that are frequently tagged by MMTV in mammary tumors were not preferentially targeted in cell culture either in mouse or in human cells; hence, we conclude that MMTV displays the most random dispersion of integration sites among retroviruses determined so far.

scholarly journals Genome-wide mapping of foamy virus vector integrations into a human cell line

2006 ◽  
Vol 87 (5) ◽  
pp. 1339-1347 ◽  
Author(s):  
Ali Nowrouzi ◽  
Marcus Dittrich ◽  
Chuck Klanke ◽  
Martin Heinkelein ◽  
Matthias Rammling ◽  
...  
Keyword(s):  
Human Genome ◽  
Integration Site ◽  
Leukemia Virus ◽  
Foamy Virus ◽  
Consensus Sequence ◽  
Cpg Islands ◽  
Retroviral Vectors ◽  
Inverse Pcr ◽  
Integration Pattern ◽  
Integration Sites

Integration-site selection by retroviruses and retroviral vectors has gained increased scientific interest. Foamy viruses (FVs) constitute a unique subfamily (Spumavirinae) of the family Retroviridae, for which the integration pattern into the human genome has not yet been determined. To accomplish this, 293 cells were transduced with FV vectors and the integration sites into the cellular genome were determined by a high-throughput method based on inverse PCR. For comparison, a limited number of murine leukemia virus (MLV) and human immunodeficiency virus (HIV) integration sites were analysed in parallel. Altogether, 628 FV, 87 HIV and 141 MLV distinct integration sites were mapped to the human genome. The sequences were analysed for RefSeq genes, promoter regions, CpG islands and insertions into cellular oncogenes. Compared with the integration-site preferences of HIV, which strongly favours active genes, and MLV, which favours integration near transcription-start regions, our results indicate that FV integration has neither of these preferences. However, once integration has occurred into a transcribed region of the genome, FVs tend to target promoter-close regions, albeit with less preference than MLV. Furthermore, our study revealed a palindromic consensus sequence for integration, which was centred on the virus-specific, four-base-duplicated target site. In summary, it is shown that the integration pattern of FVs appears to be unique compared with those of other retroviral genera.

scholarly journals HIV-1 Gag Forms Ribonucleoprotein Complexes with Unspliced Viral RNA at Transcription Sites

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1281
Author(s):  
Kevin M. Tuffy ◽  
Rebecca J. Kaddis Maldonado ◽  
Jordan Chang ◽  
Paul Rosenfeld ◽  
Alan Cochrane ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Integration Site ◽  
Leukemia Virus ◽  
Foamy Virus ◽  
Regulatory Protein ◽  
Viral Rna ◽  
Gag Protein ◽  
Ribonucleoprotein Complexes ◽  
Immunodeficiency Virus ◽  
Hiv 1

The ability of the retroviral Gag protein of Rous sarcoma virus (RSV) to transiently traffic through the nucleus is well-established and has been implicated in genomic RNA (gRNA) packaging Although other retroviral Gag proteins (human immunodeficiency virus type 1, HIV-1; feline immunodeficiency virus, FIV; Mason-Pfizer monkey virus, MPMV; mouse mammary tumor virus, MMTV; murine leukemia virus, MLV; and prototype foamy virus, PFV) have also been observed in the nucleus, little is known about what, if any, role nuclear trafficking plays in those viruses. In the case of HIV-1, the Gag protein interacts in nucleoli with the regulatory protein Rev, which facilitates nuclear export of gRNA. Based on the knowledge that RSV Gag forms viral ribonucleoprotein (RNPs) complexes with unspliced viral RNA (USvRNA) in the nucleus, we hypothesized that the interaction of HIV-1 Gag with Rev could be mediated through vRNA to form HIV-1 RNPs. Using inducible HIV-1 proviral constructs, we visualized HIV-1 Gag and USvRNA in discrete foci in the nuclei of HeLa cells by confocal microscopy. Two-dimensional co-localization and RNA-immunoprecipitation of fractionated cells revealed that interaction of nuclear HIV-1 Gag with USvRNA was specific. Interestingly, treatment of cells with transcription inhibitors reduced the number of HIV-1 Gag and USvRNA nuclear foci, yet resulted in an increase in the degree of Gag co-localization with USvRNA, suggesting that Gag accumulates on newly synthesized viral transcripts. Three-dimensional imaging analysis revealed that HIV-1 Gag localized to the perichromatin space and associated with USvRNA and Rev in a tripartite RNP complex. To examine a more biologically relevant cell, latently infected CD4+ T cells were treated with prostratin to stimulate NF-κB mediated transcription, demonstrating striking localization of full-length Gag at HIV-1 transcriptional burst site, which was labelled with USvRNA-specific riboprobes. In addition, smaller HIV-1 RNPs were observed in the nuclei of these cells. These data suggest that HIV-1 Gag binds to unspliced viral transcripts produced at the proviral integration site, forming vRNPs in the nucleus.

Modulation of human dendritic-cell function following transduction with viral vectors: implications for gene therapy

Blood ◽  
2005 ◽  
Vol 105 (10) ◽  
pp. 3824-3832 ◽  
Author(s):  
Peng H. Tan ◽  
Sven C. Beutelspacher ◽  
Shao-An Xue ◽  
Yao-He Wang ◽  
Peter Mitchell ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Mhc Class Ii ◽  
Viral Vectors ◽  
Cell Function ◽  
Leukemia Virus ◽  
Moloney Murine Leukemia Virus ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
Anemia Virus ◽  
And Function

AbstractGenetic modification of dendritic-cell (DC) function is an attractive approach to treat disease, either using mature DCs (mDCs) to immunize patients, or immature DCs (iDCs) to induce tolerance. Viral vectors are efficient at transducing DCs, and we have investigated the effect of transduction with a variety of viral vectors on the phenotype and function of DCs. Adenovirus (Ad), human immunodeficiency virus (HIV), equine anemia virus (EIAV), and Moloney murine leukemia virus (MMLV) all up-regulate costimulatory molecules and major histocompatibility complex (MHC) class II expression on DCs, as well as, in the case of Ad and lentiviral vectors, inducing production of Th1 and proinflammatory cytokines. Following transduction there is activation of double-stranded (ds) RNA-triggered pathways resulting in interferon (IFN) α/β production. In addition, the function of virally infected DCs is altered; iDCs have an increased, and mDCs a decreased, ability to stimulate a mixed lymphocyte reaction (MLR). Viral transduction of mDCs results in up-regulation of the indoleamine 2,3-dioxygenase (IDO) enzyme, which down-regulates T-cell responsiveness. Inhibition of IDO restores the ability of mDCs to stimulate an MLR, indicating that IDO is responsible for the modulation of mDC function. These data have important implications for the use of viral vectors in the transduction of DCs.

scholarly journals Prevalence of feline coronavirus, feline leukemia virus, and feline immunodeficiency virus in client-owned cats in Croatia

2021 ◽  
Vol 8 ◽  
pp. 24-38
Author(s):  
Jelena Raukar
Keyword(s):  
Veterinary Medicine ◽  
Feline Immunodeficiency Virus ◽  
Leukemia Virus ◽  
Feline Leukemia Virus ◽  
Antibody Prevalence ◽  
Blood Samples ◽  
Proviral Dna ◽  
Immunodeficiency Virus ◽  
Feline Coronavirus

This study aimed to determine prevalences for anti-FCoV antibody, FeLV antigen, FeLV proviral DNA, and anti-FIV antibody among client-owned cats from the cities of Zagreb and Varaždin in Croatia. Subjects included 106 client-owned cats tested at the Faculty of Veterinary Medicine, Vienna, Austria. Blood samples were tested with IFA for anti-FCoV antibody and IFA FCoV antibody titeres, with ELISA for FeLV p27 antigen, with PCR for FeLV proviral DNA, and with RIM for anti-FIV antibody. Prevalence of FCoV and FeLV was 41.51% and 6.60%, respectively. A coinfection with FeLV/FCoV and FIV/FCoV prevalence was 7.55% and 5.66%. No cats were coinfected with FIV and FeLV. All three viruses were detected, confirming their presence in Croatia. The seroepidemiological findings demonstrate that both feline retroviruses and feline coronavirus are important feline pathogens in Croatia.

Prevalence and Risk Factors for Heartworm Infection in Cats From Northern Florida

2003 ◽  
Vol 39 (6) ◽  
pp. 533-537 ◽  
Author(s):  
Julie K. Levy ◽  
Patti S. Snyder ◽  
Larissa M. Taveres ◽  
Jennifer L. Hooks ◽  
Mike J. Pegelow ◽  
...  
Keyword(s):  
Risk Factors ◽  
Feline Immunodeficiency Virus ◽  
Leukemia Virus ◽  
Clinical Disease ◽  
Feline Leukemia Virus ◽  
Risk Of Infection ◽  
Serological Evidence ◽  
Immunodeficiency Virus ◽  
Heartworm Infection ◽  
Adult Cats

Necropsies were performed on 630 adult cats in northern Florida to determine the prevalence and risk factors for heartworm infection in cats of this region. Heartworms were identified in 4.9% of cats, and serological evidence of heartworm exposure was present in 17% of cats. Not all cats from which heartworms were recovered were seropositive for heartworm antigen or antibody. There was no association between heartworm infection and co-infection with feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV). Male cats were at higher risk of infection with heartworm, FeLV, or FIV than were females. Because even a single heartworm can cause clinical disease or death in cats, the authors conclude that cats in this region should receive heartworm prophylaxis to prevent heartworm infection.

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