Role of key amino acids in the transmembrane domain of the Newcastle disease virus fusion protein

Abstract

Newcastle disease (ND), caused by the Newcastle disease virus (NDV), is transmitted by poultry with severe infectivity and a high fatality rate. The fusion (F) protein on the NDV envelope facilitates the merger of the viral and host cell membranes with the help of the homologous hemagglutininneuraminidase protein (HN). The transmembrane (TM) domains of viral fusion proteins are typically required for fusion, but the key amino acids in NDV F TM domains have not been identified. Sitedirected mutagenesis was utilized to change the conserved amino acids at 500, 501, 502, 505, 510, 513, 516, 519, and 520 to alanine. It was found that mutants L519 and V520 had an interrupted protein expression, decreased to below 10%, and mutants A500, I505, V513, and V516 had a hypoactive impact on fusion activity, decreased to 85.38%, 67.05%, 55.38% and 51.13% of wt F, respectively. The results indicated that the TM domain plays a vital part in the fusion activity of the NDV F protein.

Development of a novel cholesterol tag-based system for trans-membrane transport of protein drugs

“…In terms of diagnosis and treatment of some refractory diseases, a crucial task is to explore the cytosolic targets associated with cell necrocytosis, energy metabolism, and protein expression (5). During the development of a novel therapy, we sometimes need to deliver therapeutic proteins or drugs from extracellular fluid to the cytoplasm (6). However, cytosolic delivery of therapeutic proteins is usually hampered by cell membrane obstruction, endocytic sequestration, and lysosomal breakdown, which present notable barriers for approaching those intracellular targets (7)(8)(9).…”

The Influence of Newcastle Disease Virus Major Proteins on Virulence

“…This F 0 cleavage is necessary for virus infection. The transmembrane (TM) domains of viral F proteins play a vital role in NDV F protein fusion activity [34] . The oncolytic activity of NDV has been traced to the minor multifunctional protein HN, and the HN protein has been shown to induce apoptosis in chicken embryo fibroblast cells [35] .…”