Viral Interactions with Adaptor-Protein Complexes: A Ubiquitous Trait among Viral Species

Abstract

Numerous viruses hijack cellular protein trafficking pathways to mediate cell entry or to rearrange membrane structures thereby promoting viral replication and antagonizing the immune response. Adaptor protein complexes (AP), which mediate protein sorting in endocytic and secretory transport pathways, are one of the conserved viral targets with many viruses possessing AP-interacting motifs. We present here different mechanisms of viral interference with AP complexes and the functional consequences that allow for efficient viral propagation and evasion of host immune defense. The ubiquity of this phenomenon is evidenced by the fact that there are representatives for AP interference in all major viral families, covered in this review. The best described examples are interactions of human immunodeficiency virus and human herpesviruses with AP complexes. Several other viruses, like Ebola, Nipah, and SARS-CoV-2, are pointed out as high priority disease-causative agents supporting the need for deeper understanding of virus-AP interplay which can be exploited in the design of novel antiviral therapies.

Role of adaptin protein complexes in intracellular trafficking and their impact on diseases

“…Intracellular trafficking is used by viruses to mediate their entry into host cells or Comment [SJ5]: Reviewer 1, comment 2. "The authors are suggested to introduce the AP roles in the cell in detail according to the figures which would help readers understand the manuscript" for AP5 promote their replication [270]. A deficiency in intracellular transport can cause severe genetic diseases [271] while it is also putatively a target for treating cancer [272].…”

“…Clathrin [277] LLNLD [277] μ1 HIV-Nef [278] YXXØ, X is any amino acid, Ø is a bulky hydrophobic amino acid [270,279];…”

“…EXXXLL [278] σ1 DXXLL [270,279] AP2 α Eps15 [280], epsin 1, amphiphysin I, AP180 [281], auxilin, dynamin 1 and 2, SJ170 [282], stonin2 [283], Clathrin [276] DPW; DPF [280]; FXDXF [281]; WXXF [282]; LLDLL [276]; WVXF [283] β2…”

“…Clathrin [277] LLNLD [277] μ2 HIV-Nef [278], stonin2 [283] YXXØ, [270,279]; EXXXLL Figure 1. AP complexes with their known or suggested role in cells.…”

“…Understanding and controlling intracellular trafficking can be crucialaspects in disease treatments. For example, intracellular trafficking can be used by viruses to mediate their entry into host cells or promote their replication [ 270 ], a deficiency in intracellular transport can cause severe genetic diseases [ 271 ] while it is also putatively a target for treating cancer [ 272 ]. Moreover, endocytosis is an important feature that should be considered in drug delivery [ 273 ].…”