Department of Molecular and Cellular Biochemistry, College of Medicine University of Kentucky Biomedical Biological Sciences Research Bldg, 741 South Limestone Street, Lexington, KY, USA.
J Gen Virol. 2020 May;101(5):467-472. doi: 10.1099/jgv.0.001399. Epub 2020 Feb 25.
The paramyxoviruses Hendra virus (HeV) and parainfluenza virus 5 (PIV5) require the fusion (F) protein to efficiently infect cells. For fusion to occur, F undergoes dramatic, essentially irreversible conformational changes to merge the viral and cell membranes into a continuous bilayer. Recently, a transmembrane (TM) domain leucine/isoleucine (L/I) zipper was shown to be critical in maintaining the expression, stability and pre-fusion conformation of HeV F, allowing for fine-tuned timing of membrane fusion. To analyse the effect of the TM domain L/I zipper in another paramyxovirus, we created alanine mutations to the TM domain of PIV5 F, a paramyxovirus model system. Our data show that while the PIV5 F TM L/I zipper does not significantly affect total expression and only modestly affects surface expression and pre-fusion stability, it is critical for fusogenic activity. These results suggest that the roles of TM L/I zipper motifs differ among members of the family .
副粘病毒亨德拉病毒（HeV）和副流感病毒 5（PIV5）需要融合（F）蛋白才能有效地感染细胞。为了发生融合，F 经历了剧烈的、本质上不可逆转的构象变化，将病毒和细胞膜融合成连续的双层。最近，跨膜（TM）结构域亮氨酸/异亮氨酸（L/I）拉链被证明在维持 HeV F 的表达、稳定性和预融合构象方面至关重要，从而可以精细地调节膜融合的时间。为了分析 TM 结构域 L/I 拉链在另一种副粘病毒中的作用，我们在副粘病毒模型系统 PIV5 F 的 TM 结构域中创建了丙氨酸突变。我们的数据表明，尽管 PIV5 F TM L/I 拉链对总表达的影响不大，仅适度影响表面表达和预融合稳定性，但它对融合活性至关重要。这些结果表明，TM L/I 拉链基序在家族成员中的作用不同。
