Role of Protein–Lipid Interactions in Viral Entry

Abstract

description, lipid raft has generated equal levels of enthusiasm and controversy in the research community. [1,5] This controversy arises from the lack of suitable tools to unravel the existence of such nanostructures in living organisms at resting state. [5][6][7] Despite this long-lasting controversy, what we can ascertain is that the alteration of membrane physicochemical properties such as curvature, elasticity, or fluidity can have a direct effect in membrane protein properties and function, and finally, in viral infectivity. [8,9] Therefore, viruses are a clear example of how cell membrane physicochemical properties are of high evolutionary relevance, as they are exploited by these pathogens in the infection cycle.Viruses are obligatory intracellular parasites that are simple in structure and compositions but hijack the host cellular mechanisms to ensure viral infection and progression. Naked viruses contain a genome encased in a protein shell called capsid, which in the case of enveloped viruses is surrounded by a host cell-derived lipid membrane.The viral entry process is a complex and determinant step necessary for establishing viral infection since viral replication occurs exclusively inside the host cell. It compiles sequential events starting from viral attachment to the host cell to penetration to cell cytoplasm. Attachment of virus particles to host cell molecules that act as cellular receptors, such as lipid or proteins, determines cellular tropism and, therefore, specificity. After adhesion, virus penetration occurs either at the plasma membrane or the endomembrane system upon environment acidification. For enveloped viruses, transfer is achieved by fusion of the viral and cellular membranes. The fusion event is catalyzed by the fusion protein, which engages to receptor(s) triggering a conformational change necessary to induce fusion between both membranes. This conformational change can occur in the plasma membrane at neutral pH or in the endosomal membranes upon endosome acidification. In the case of naked viruses, endosome acidification is needed to trigger conformational changes of the viral protein required in order to transiently destabilize the target membrane without compromising its overall integrity. [10][11][12] Virus entry is not a passive process, since productive entry, and downstream events rely on normal cellular processes including endocytosis (clathrin-mediated, clathrin-independent pathway, raft-dependent pathways, and macropinocytosis), vesicular trafficking, and membrane fusion, all of which involve dynamic membrane processes. [10,13] The fact that lipid interactions, including membrane envelopment, membrane fusion, and membrane remodeling are crucial for successful replication of many viruses triggered studies on compounds that either affect lipid biosynthesis,The viral entry consists of several sequential events that ensure the attachment of the virus to the host cell and the introduction of its genetic material for the continuation of the replication cycle. Both cellular an...

Research on the metabolic regulation mechanism of Yangyin Qingfei decoction plus in severe pneumonia caused by Mycoplasma pneumoniae in mice

“…In order to investigate the YQDP’s mechanism of action on SMPP mice further, we used UPLC-MS/MS technology to do a metabolomic study of lung tissue samples from normal, model, and YQDP-treated groups. This study screened 47 differential metabolites that changed after the addition of YQDP, mostly lipids, nucleosides, and fatty acids, which play important roles in inhibiting the immune inflammatory process and participating in multiple inflammatory processes ( Das, 2021 ; Nieto-Garai et al, 2022 ). The research discovered that while YQDP intervention altered various endogenous metabolites in the model group’s lung tissue, it also altered pathways including the metabolism of α-linolenic acid, sphingolipids, glycerophospholipids, arachidonic acid, and unsaturated fatty acid biosynthesis, which had a therapeutic effect on SMPP mice.…”

Viral Membrane Fusion: A Dance Between Proteins and Lipids

“…As discussed above, BMP, which is enriched in LE, enhances endosomal fusion of influenza A virus, DENV, yellow fever virus, and Japanese encephalitis virus, where studied at the fusion pore stage ( 21 , 22 , 115 ). Similarly, at the plasma membrane, HIV promotes nonapoptotic phosphatidylserine exposure to increase charge on the fusing membrane and decrease some of the energetic cost of headgroup dehydration ( 117 , 118 ).…”

“…While the influence of cell membrane nanodomains has been explored for many enveloped viruses ( 117 , 128 , 129 ), the most thoroughly studied is regarding HIV. Within phase-separated plasma membranes, the HIV receptor, CD4, preferentially partitions within ordered domains while its coreceptor, CCR5, partitions to the interface of ordered and disordered domains ( 130 ) ( Figure 4a ).…”

The Mechanisms of Ferroptosis and the Applications in Tumor Treatment: Enemies or Friends?

“…The free radicals and hyperoxides generated after the redox reaction of Fe 2+ and Fe 3+ can react with Polyunsaturated fatty acids (PUFAs) containing phospholipids (PLs) in the cell membrane to facilitate the spread of lipid peroxidation on the cell membrane. This process produces lots of ROS and induces cell ferroptosis (Doll and Conrad, 2017;Ruizde-Angulo et al, 2020;Nieto-Garai et al, 2022). In addition, irondependent lipid peroxidation can be attenuated by GPX4, radical trapping protein removal, ferroptosis-specific inhibitors, and iron chelation.…”