Biochemical characteristics of functional domains using feline foamy virus integrase mutants

We constructed deletion mutants and seven point mutants bypolymerase chain reaction to investigate the specificity of felinefoamy virus integrase functional domains. Complementationreactions were performed for three enzymatic activities such as3’-end processing, strand transfer, and disintegration. Thecomplementation reactions with deletion mutants showedseveral activities for 3’-end processing and strand transfer. Theconserved central domain and the combination of the N-terminalor C-terminal domains increased disintegration activitysignificantly. In the complementation reactions between deletionand point mutants, the combination between D107V anddeletion mutants revealed 3’-end processing activities, but thecombination with others did not have any activity, includingstrand transfer activities. Disintegration activity increased evenly,except the combination with glutamic acid 200. These resultssuggest that an intact central domain mediates enzymaticactivities but fails to show these activities in the absence of theN-terminal or C-terminal domains. [BMB Reports 2013; 46(1):53-58

Cellular and viral determinants of retroviral nuclear entry

Retroviruses must integrate their cDNA into the host genome to generate proviruses. Viral DNA-protein complexes interact with cellular proteins and produce pre-integration complexes (PICs), which carry the viral genome and cross the nuclear pore channel to enter the nucleus and integrate viral DNA into host chromosomal DNA. If the reverse transcripts fail to integrate, linear or circular DNA species such as 1- and 2-long-terminal-repeats (1-LTRs and 2-LTRs, respectively) are generated. Such complexes encounter numerous cellular proteins in the cytoplasm, which restrict viral infection and protect the nucleus. To overcome host cell defenses, the pathogens have evolved several evasion strategies. Viral proteins often contain nuclear localization signals (NLSs), allowing entry into the nucleus. Among more than 1000 proteins identified as required for HIV infection by RNA interference screening, karyopherins, cleavage and polyadenylation specific factor 6, and nucleoporins have been predominantly studied. This review discusses current opinions about the synergistic relationship between the viral and cellular factors involved in nuclear import, with focus on the unveiled mysteries of the host-pathogen interaction, and highlights novel approaches to pinpoint therapeutic targets.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Structural and Functional Insights into Foamy Viral Integrase

Successful integration of retroviral DNA into the host chromosome is an essential step for viral replication. The process is mediated by virally encoded integrase (IN) and orchestrated by 3'-end processing and the strand transfer reaction. In vitro reaction conditions, such as substrate specificity, cofactor usage, and cellular binding partners for such reactions by the three distinct domains of prototype foamy viral integrase (PFV-IN) have been described well in several reports. Recent studies on the three‑dimensional structure of the interacting complexes between PFV-IN and DNA, cofactors, binding partners, or inhibitors have explored the mechanistic details of such interactions and shown its utilization as an important target to develop anti-retroviral drugs. The presence of a potent, non-transferable nuclear localization signal in the PFV C-terminal domain extends its use as a model for investigating cellular trafficking of large molecular complexes through the nuclear pore complex and also to identify novel cellular targets for such trafficking. This review focuses on recent advancements in the structural analysis and in vitro functional aspects of PFV-IN

Semicircular Horizontal Approach in Breast Reduction: Clinical Experience in 38 Cases

Background Various techniques are used for performing breast reduction. Wise-pattern and vertical scar techniques are the most commonly employed approaches. However, a vertical scar in the mid-lower breast is prominent and aesthetically less pleasant. In contrast, a semicircular horizontal approach does not leave a vertical scar in the mid breast and transverse scars can be hidden in the inframammary fold. In this paper, we describe the experiences and results of semicircular horizontal breast reductions performed by a single surgeon. Methods Between September 1996 and October 2013, our senior author used this technique in 38 cases in the US and at our institution. We used a superiorly based semicircular incision, where the upper skin paddle was pulled down to the inframammary fold with the nipple-areola complex pulled through the keyhole. Results The average total reduction per breast was 584 g, ranging from 286 to 794 g. The inferior longitudinal pedicle was used in all the cases. The average reduction of the distance from the sternal notch to the nipple was 13 cm (range, 11-15 cm). The mean decrease in the bra cup size was 1.7 cup sizes (range, a decrease of 1 to 3). We obtained very satisfactory results with a less noticeable scar, no complication such as necrosis of the nipple or the skin flap, wound infection, aseptic necrosis of the breast tissue, or wound dehiscence. One patient had a small hematoma that resolved spontaneously. Conclusions This technique is straightforward and easy to learn, and offers a safe, effective, and predictable way for treating mammary hypertrophy