Addicted to sugar: roles of glycans in the order Mononegavirales

Abstract

Glycosylation is a biologically important protein modification process by which a carbohydrate chain is enzymatically added to a protein at a specific amino acid residue. This process plays roles in many cellular functions, including intracellular trafficking, cell-cell signaling, protein folding and receptor binding. While glycosylation is a common host cell process, it is utilized by many pathogens as well. Protein glycosylation is widely employed by viruses for both host invasion and evasion of host immune responses. Thus better understanding of viral glycosylation functions has potential applications for improved antiviral therapeutic and vaccine development. Here, we summarize our current knowledge on the broad biological functions of glycans for the Mononegavirales, an order of enveloped negative-sense single-stranded RNA viruses of high medical importance that includes Ebola, rabies, measles and Nipah viruses. We discuss glycobiological findings by genera in alphabetical order within each of eight Mononegavirales families, namely, the bornaviruses, filoviruses, mymonaviruses, nyamiviruses, paramyxoviruses, pneumoviruses, rhabdoviruses and sunviruses.

Fig. 1.

Glycosylation schematic. (A) Diagram of high-mannose (left), complex (center) and hybrid (right) N-glycans. (B) Diagram of the four main O-glycan core types. (C) Differences between N- and O-glycans.

Fig. 2.

Diagram of the Mononegavirales order. The phylogenetic tree was built after obtaining the RNA polymerase/large protein sequences of the viruses from the NCBI Protein Database. The protein sequences were aligned by using the COBALT Multiple alignment tool, by the fast-minimum evolution method and visualized using Figtree. The virus names and GenBank accession numbers are as follows: Bornaviridae—Borna disease virus 1 (BoDV-1; NP_042024), Filoviridae—Marburg virus (MARV; YP_001531159), Lloviu virus (LLOV; YP_004928143.1), Zaire ebola virus virus (EBOV; NP_066251.1), Mymonaviridae—Sclerotinia sclerotiorum negative-stranded RNA virus 1 (SsNSRV-1; 20996185), Nyamiviridae—Nyamanini virus (NYMV; YP_002905337), Pteromalus puparum negative-strand RNA virus 1 (PpNSRV-1; APL97667.1), Soybean cyst nematode virus (SbCNV-1; AEF56729), Paramyxoviridae—Avian paramyxovirus 1 (APMV-1; NP_071471), measles virus (MeV; NP_056924), Mumps virus (MuV; NP_054714), Nipah virus (NiV; AAK50546.1), Sendai virus (SeV; NP_056879), Atlantic salmon paramyxovirus (AsaPV; ABX57743.1), Fer-de-Lance virus (FDLV; AAN18266.1), Pneumoviridae—human respiratory syncytial virus-A2 (HRSV-A2; NP_056866), Avian metapneumovirus (AMPV; YP_443845), Rhabdoviridae—rabies virus (RABV; NP_056797), Tupaia virus (TUPV; YP_238534.1), Drosophila affinis sigmavirus (DAffSV; KR822811.1), pike fry rhabdovirus (PFRV; ACP28002.1), Niakha virus (NIAV; AGO44084.1), vesicular stomatitis Indian virus (VSIV; NP_041716), eel virus European X (EVEX; AHD46104.1), bovine ephemeral fever virus (BEFV; NP_065409), Coastal Plains virus (CPV; ADG86364.1), lettuce necrotic yellow virus (LNYV), orchid fleck virus (OFV; NC_009609.1), Datura yellow vein virus (DYVV; AKH61406.1), lettuce big-vein-associated virus (LBVaV; JN710440.1), Arboretum virus (ABTV; AHU86500.1), Flanders virus (FLAV; AAN73288.1), Kumasi rhabdovirus (KRV; YP_009177014.1), Curionopolis virus (CURV; AIE12119.1), infectious hematopoietic necrosis virus (IHNV; NP_042681), Sunshinevirus—Sunshine Coast virus (SunCV; YP_009094051.1).

Fig. 3.

Diagram of the viral life cycle. (A) Virions bind to host cell receptors (black), facilitating viral entry into the cell. Once within the cell, transcription and replication occur. This allows the production of viral proteins, which are processed and trafficked through the cell using host cell machinery (endoplasmic reticulum and Golgi apparatus). Viral proteins and RNA are packaged into new virions, which are then released from the cell. These virions can then interact with the host immune system. (B) Infected cells can express viral proteins on their cell membranes, which can react with cell receptors on neighboring naïve cells, causing cell–cell fusion.