• Journal of Microbiology and Biotechnology
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• v.30 no.9
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• pp.1273-1281
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• 2020

Due to the broad host suitability of viral vectors and their high gene delivery capacity, many researchers are focusing on viral vector-mediated gene therapy. Among the retroviruses, foamy viruses have been considered potential gene therapy vectors because of their non-pathogenicity. To date, the prototype foamy virus is the only retrovirus that has a high-resolution structure of intasomes, nucleoprotein complexes formed by integrase, and viral DNA. The integration of viral DNA into the host chromosome is an essential step for viral vector development. This process is mediated by virally encoded integrase, which catalyzes unique chemical reactions. Additionally, recent studies on foamy virus integrase elucidated the catalytic functions of its three distinct domains and their effect on viral pathogenicity. This review focuses on recent advancements in biochemical, structural, and functional studies of foamy virus integrase for gene therapy vector research.

• Journal of Microbiology and Biotechnology
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• v.20 no.6
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• pp.968-973
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• 2010

In order to study its biochemical properties, the integrase (IN) protein of feline foamy virus (FFV) was overexpressed in Escherichia coli, purified by two-step chromatography, (Talon column and heparin column), and characterized in biochemical aspects. For the three enzymatic reactions of the 3'-processing, strand transfer, and disintegration activities, the $Mn^{2+}$ ion was essentially required as a cofactor. Interestingly, $Co^{2+}$ and $Zn^{2+}$ ions were found to act as effective cofactors, whereas other transition elements such as $Ni^{2+}$, $Cu^{2+}$, $La^{3+}$, $Y^{3+}$, $Cd^{2+}$, $Li^{1+}$, $Ba^{2+}$, $Sr^{2+}$, and $V^{3+}$ were not. Regarding the substrate specificity, FFV IN has low substrate specificities as it cleaved in a significant level prototype foamy virus (PFV) U5 LTR substrate as well as FFV U5 LTR substrate, whereas PFV IN did not. Finally, the 3'-processing activity was observed in high concentrations of several solvents such as CHAPS, glycerol, Tween 20, and Triton X-100, which are generally used for dissolution of chemicals in inhibitor screening. Therefore, in this first report showing its biochemical properties, FFV IN is proposed to have low specificities on the use of cofactor and substrate for enzymatic reaction as compared with other retroviral INs.

• Journal of Microbiology and Biotechnology
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• v.27 no.2
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• pp.380-387
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• 2017

The foamy viruses are currently considered essential for development as vectors for gene delivery. Previous studies demonstrated that prototype foamy virus (PFV) can infect and replicate prevalently in a variety of cell types for its exclusive replication strategy. However, the virus-host interaction, especially PFV-transportin3 (TNPO3), is still poorly understood. In our investigation of the role of TNPO3 in PFV infection, we found lower virus production in TNPO3 knockdown (KD) cells compared with wild-type 293T cells. PCR analysis revealed that viral DNAs were mostly altered to circular forms: both 1-long terminal repeat (1-LTR) and 2-LTR in TNPO3 KD cells. We therefore suggest that TNPO3 is required for successful PFV replication, at least at/after the nuclear entry step of viral DNA. These findings highlight the obscure mysteries of PFV-host interaction and the requirement of TNPO3 for productive infection of PFV in 293T cells.

• IMMUNE NETWORK
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• v.23 no.4
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• pp.28.1-28.20
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• 2023

Lipid accumulation in macrophages is a prominent phenomenon observed in atherosclerosis. Previously, intimal foamy macrophages (FM) showed decreased inflammatory gene expression compared to intimal non-foamy macrophages (NFM). Since reprogramming of lipid metabolism in macrophages affects immunological functions, lipid profiling of intimal macrophages appears to be important for understanding the phenotypic changes of macrophages in atherosclerotic lesions. While lipidomic analysis has been performed in atherosclerotic aortic tissues and cultured macrophages, direct lipid profiling has not been performed in primary aortic macrophages from atherosclerotic aortas. We utilized nanoflow ultrahigh-performance liquid chromatography-tandem mass spectrometry to provide comprehensive lipid profiles of intimal non-foamy and foamy macrophages and adventitial macrophages from Ldlr^-/- mouse aortas. We also analyzed the gene expression of each macrophage type related to lipid metabolism. FM showed increased levels of fatty acids, cholesterol esters, phosphatidylcholine, lysophosphatidylcholine, phosphatidylinositol, and sphingomyelin. However, phosphatidylethanolamine, phosphatidic acid, and ceramide levels were decreased in FM compared to those in NFM. Interestingly, FM showed decreased triacylglycerol (TG) levels. Expressions of lipolysis-related genes including Pnpla2 and Lpl were markedly increased but expressions of Lpin2 and Dgat1 related to TG synthesis were decreased in FM. Analysis of transcriptome and lipidome data revealed differences in the regulation of each lipid metabolic pathway in aortic macrophages. These comprehensive lipidomic data could clarify the phenotypes of macrophages in the atherosclerotic aorta.

• BMB Reports
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• v.46 no.1
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• pp.53-58
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• 2013

We constructed deletion mutants and seven point mutants by polymerase chain reaction to investigate the specificity of feline foamy virus integrase functional domains. Complementation reactions were performed for three enzymatic activities such as 3'-end processing, strand transfer, and disintegration. The complementation reactions with deletion mutants showed several activities for 3'-end processing and strand transfer. The conserved central domain and the combination of the N-terminal or C-terminal domains increased disintegration activity significantly. In the complementation reactions between deletion and point mutants, the combination between D107V and deletion mutants revealed 3'-end processing activities, but the combination with others did not have any activity, including strand transfer activities. Disintegration activity increased evenly, except the combination with glutamic acid 200. These results suggest that an intact central domain mediates enzymatic activities but fails to show these activities in the absence of the N-terminal or C-terminal domains.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.49 no.6
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• pp.360-364
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• 2023

Xanthogranulomatous inflammation (XGI) is an uncommon type of chronic inflammation and is histologically characterized by foamy histiocytes and giant cells. The most common sites of occurrence are kidneys and gallbladder. The etiology remains controversial. Involvement of the lower jaw bone is rare. In this study, we report a case of XGI presenting in the lower jaw.

• Journal of Veterinary Science
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• v.25 no.1
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• pp.14.1-14.5
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• 2024

An adult female ringed seal died suddenly and was subsequently examined for diagnostic purposes. The animal's lungs demonstrated mild non-collapsibility and multifocal white to yellow patches. Histopathological examination revealed multifocal pulmonary histiocytosis. Alveoli were filled with numerous foamy macrophages cytoplasm and scattered multinucleated giant cells containing cholesterol clefts. The foamy cytoplasm of the macrophages stained with oil red O stain. Further, lipid droplets within the cytoplasm were detected by electron microscopy. To the author's knowledge, this is the first case report describing the histochemical staining and electron microscopic findings associated with endogenous lipid pneumonia in ringed seal.

• Journal of Microbiology and Biotechnology
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• v.18 no.6
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• pp.1044-1049
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• 2008

In order to study functional nucleotides in prototype foamy virus (PFV) DNA on specific recognition by PFV integrase (IN), we designed chimeric U5 long terminal repeat (LTR) DNA substrates by exchanging comparative sequences between human immunodeficiency virus type-1 (HIV-1) and PFV U5 LTRs, and investigated the 3'-end processing reactivity using HIV-1 and PFV INs, respectively. HIV-1 IN recognized the nucleotides present in the fifth and sixth positions at the 3'-end of the substrates more specifically than any other nucleotides in the viral DNA. However, PFV IN recognized the eighth and ninth nucleotides as distinctively as the fifth and sixth nucleotides in the reactions. In addition, none of the nucleotides present in the twelfth, sixteenth, seventeenth, eighteenth, nineteenth, and twentieth positions were not differentially recognized by HIV-1 and PFV INs, respectively. Therefore, our results suggest that the functional nucleotides that are specifically recognized by its own IN in the PFV U5 LTR are different from those in the HIV-1 U5 LTR in aspects of the positions and nucleotide sequences. Furthermore, it is proposed that the functional nucleotides related to the specific recognition by retroviral INs are present inside ten nucleotides from the 3'-end of the U5 LTR.

• YAKHAK HOEJI
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• v.52 no.2
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• pp.125-130
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• 2008

The long terminal repeat (LTR) of retroviral DNA genome plays an important role in the integration process by providing substrate recognition site for viral integrase (IN). The dinucleotide CA near the 3'-end of the LTR termini is completely conserved among retoviruses. In order to study specificity of interaction between prototype foamy virus (PFV) IN and its U5 LTR DNA, the effect of mutagenesis of the CA sequence was investigated by studying reactivity of PFV IN to the mutant LTR substrates. Replacement of only the C or the A allowed 60 to 100% of the reactivity of the wild type LTR substrate. In addition, replacement of the C and the A showed 50 to 80% of the reactivity of the wild type LTR substrate, indicating that PFV IN has less specificity on the conserved CA sequence when it is compared to the other retroviral INs. Therefore it is suggested that PFV IN is less dependent on the conserved sequence of LTR termini for its enzymatic reaction.

• The Korean Journal of Cytopathology
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• v.9 no.1
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• pp.95-98
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• 1998

Papillary renal cell carcinoma (RCC) is an uncommon subtype of RCC that has distinctive gross, histologic, and cytogenetic features. The cytologic features of FNA are abundant papillary clusters and relatively few single cells. The cells are usually small and contain uniform nuclei; numerous macrophages with foamy cytoplasm are often found in the background. We describe a case of papillary renal cell carcinoma evaluated by fine needle aspiration cytology(FNAC) in a 42 year-old man. The smear showed a few papillary clusters and numerous macrophages with foamy cytoplasm in the background. With adequate cellularity, papillary RCC can be distinguished reliably from non-papillary RCC by FNAC.