Glycans on viral envelope glycoproteins play important roles in virus biology, with specific functions identified in various stages of viral infection (Table I and Figure 2). As previously mentioned, glycosylation is generally required for progeny formation and infectivity for many viruses (Knowles and Person 1976; Leavitt et al. 1977; Olofsson and Lycke 1980; Herrler and Compans 1983; Lambert and Pons 1983; Mann et al. 1983; Kuhn et al. 1988; Li et al. 2006; Reszka et al. 2010; Mathys and Balzarini 2015; Shrivastava-Ranjan et al. 2016; Mossenta et al. 2017). In some cases, mature N-glycans in particular are necessary for proper viral particle formation and release (Datema et al. 1984). As in human proteins, N-linked glycosylation is critical for proper folding of viral proteins (Land and Braakman 2001; Zai et al. 2013; Wu et al. 2017), and, in some cases, viral protein secretion (Hu et al. 1995; Lu et al. 1997; Yoshii et al. 2013; Mossenta et al. 2017). Drugs targeting glycoprotein maturation and exhibiting a favorable therapeutic ratio can therefore be used to combat viral infections, where no other therapeutics are available (Miller et al. 2012). Most importantly, N- and O-linked glycans shield immunodominant epitopes from immune recognition (Francica et al. 2010; Helle et al. 2011; Sommerstein et al. 2015; Behrens et al. 2016; Gram et al. 2016; Walls et al. 2016). In addition to general functions, specific types of glycans on viral glycoproteins often affect receptor binding and cell fusion (Lin et al. 2003; Lozach et al. 2003; Gramberg et al. 2005; Davis et al. 2006; Miller et al. 2008; Chen et al. 2014; Phoenix et al. 2016; Wang et al. 2016). Moreover, it is becoming increasingly clear that distinct glycans play separate roles in various stages of the viral cycle (Goffard et al. 2005; Falkowska et al. 2007; Helle et al. 2010; Wang et al. 2013, 2017; Lennemann et al. 2014; Bradel-Tretheway et al. 2015; Luo et al. 2015; Orlova et al. 2015; Wu et al. 2017). Some site-specific functions of viral glycosylation have been assigned for both N- and O-linked glycans mostly by site-directed mutagenesis studies. Identified roles of glycans within various stages of the viral cycle will be discussed in the following sections.
Table I. Glycosylation of viral proteins of human eveloped viruses
Abbr. Virus name Family Genus Genome N-glycosylateda O-glycosylateda Binding/entry/haemagglutination/infectivitya Spreada Formation/release/yield/protein transporta Immune responsea Protein–protein interaction and other functionsa
LASV Lassa virus Arenaviridae Arenavirus (−)ssRNA Shrivastava-Ranjan et al. (2016) Sommerstein et al. (2015)
MACV Machupo virus Arenaviridae Arenavirus (−)ssRNA Bowden et al. (2009);
INKV Inkoo virus Bunyaviridae Orthobunyavirus (−)ssRNA Pesonen, Ronnholm et al. (1982)
RVFV Rift Valley fever virus Bunyaviridae Phlebovirus (−)ssRNA Phoenix et al. (2016) Phoenix et al. (2016)
UUKV Uukuniemi virus Bunyaviridae Phlebovirus (−)ssRNA Pesonen, Kuismanen et al. (1982)
HCoV Human coronavirus Coronaviridae Alphacoronavirus (+)ssRNA Walls et al. (2016)
MHV Mouse hepatitis virusb Coronaviridae Betacoronavirus (+)ssRNA Niemann et al. (1982) Niemann et al. (1982); Niemann et al. (1984); Locker et al. (1992) Niemann et al. (1982)
SARS-CoV SARS-related human coronavirus Coronaviridae Betacoronavirus (+)ssRNA Gramberg et al. (2005)
EBOV Ebola virus Filoviridae Ebolavirus (−)ssRNA Jeffers et al. (2002); Ritchie et al. (2010); Collar et al. (2016) Jeffers et al. (2002); Ritchie et al. (2010); Collar et al. (2016) Lin et al. (2003); Takada et al. (2004); Gramberg et al. (2005); Lennemann et al. (2014) Wang et al. (2017) Dowling et al. (2007); Francica et al. (2010); Noyori et al. (2013); Lennemann et al. (2014)
MARV Marburg virus Filoviridae Marburgvirus (−)ssRNA Feldmann et al. (1991) Feldmann et al. (1991) Becker et al. (1995); Gramberg et al. (2005) Noyori et al. (2013)
DENV Dengue virus Flaviviridae Flavivirus (+)ssRNA Miller et al. (2008); Dubayle et al. (2015); Lei et al. (2015) Davis et al. (2006); Miller et al. (2008) Rouvinski et al. (2015)
JEV Japanese encephalitis virus Flaviviridae Flavivirus (+)ssRNA Zai et al. (2013) Wang et al. (2016) Zai et al. (2013)
MVEV Murray Valley encephalitis virus Flaviviridae Flavivirus (+)ssRNA Blitvich et al. (2001)
TBEV Tick-borne encephalitis virus Flaviviridae Flavivirus (+)ssRNA Yoshii et al. (2013) Yoshii et al. (2013)
WNV West Nile virus Flaviviridae Flavivirus (+)ssRNA Davis et al. (2006) Whiteman et al. (2010) Li et al. (2006)
ZIKV Zika virus Flaviviridae Flavivirus (+)ssRNA Mossenta et al. (2017) Mossenta et al. (2017)
HCV Hepatitis C virus Flaviviridae Hepacivirus (+)ssRNA Iacob et al. (2008) Brautigam et al. (2013) Lozach et al. (2003); Goffard et al. (2005); Falkowska et al. (2007); Helle et al. (2010); Chen et al. (2014) Fournillier et al. (2001); Goffard et al. (2005); Helle et al. (2010); Reszka et al. (2010); Orlova et al. (2015) Fournillier et al. (2001); Falkowska et al. (2007); Liu et al. (2007); Brown et al. (2010); Helle et al. (2010); Anjum et al. (2013); Zhao et al. (2014); Li et al. (2016) Meunier et al. (1999); Goffard et al. (2005); Orlova et al. (2015)
HBV Hepatitis B virus Hepadnaviridae Orthohepadnavirus dsDNA-RT Schmitt et al. (1999) Schmitt et al. (1999) Lu et al. (1997); Ito et al. (2010); Julithe et al. (2014) Julithe et al. (2014); Hyakumura et al. (2015)
HCMV (HHV-5) Human cytomegalovirus (human herpesvirus 5) Herpesviridae Cytomegalovirus dsDNA Kim et al. (1976)c; Britt and Vugler (1989); Kaye et al. (1992); Al-Barazi and Colberg-Poley (1996); Jones et al. (1996); Margulies et al. (1996); Maidji et al. (1998); Huber and Compton (1999); Mullberg et al. (1999); Rehm et al. (2001); Gewurz et al. (2002); Theiler and Compton (2002); Griffin et al. (2005); Margulies and Gibson (2007); Lin et al. (2008); Stanton et al. (2010); Engel et al. (2011); Gabaev et al. (2014); Geyer et al. (2014); Cavaletto et al. (2015) Britt and Vugler (1989); Kari et al. (1992); Theiler and Compton (2002); Gabaev et al. (2014); Geyer et al. (2014); Bagdonaite et al. (2016) Kropff et al. (2012)
EBV (HHV-4) Epstein-Barr virus (human herpesvirus 4) Herpesviridae Lymphocryptovirus dsDNA Edson and Thorley-Lawson (1983); Gong et al. (1987); Serafini-Cessi et al. (1989); Gong and Kieff (1990); Nolan and Morgan (1995); Paulsen et al. (2005); de Turenne-Tessier and Ooka (2007); Gore and Hutt-Fletcher (2009) Gong et al. (1987)c; Serafini-Cessi et al. (1989); Nolan and Morgan (1995); Borza and Hutt-Fletcher (1998); de Turenne-Tessier and Ooka (2007); Xiao et al. (2007); Bagdonaite et al. (2016) D’Arrigo et al. (2013); Gram et al. (2016)
KSHV (HHV-8) Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) Herpesviridae Rhadinovirus dsDNA Chandran et al. (1998)c; Pertel et al. (1998); Li et al. (1999); Zhu et al. (1999); Baghian et al. (2000); Wu et al. (2000); Chung et al. (2002); Koyano et al. (2003); Dela Cruz et al. (2004); Meads and Medveczky (2004); Dela Cruz et al. (2009); Wu et al. (2015) Zhu et al. (1999); Wu et al. (2000) Dela Cruz et al. (2004); Wu et al. (2015)d
HHV-6 Human herpesvirus 6 Herpesviridae Roseolovirus dsDNA Okuno et al. (1990); Foa-Tomasi et al. (1992); Okuno et al. (1992); Pfeiffer et al. (1995)c Cardinali et al. (1998); Torrisi et al. (1999)
HHV-7 Human herpesvirus 7 Herpesviridae Roseolovirus dsDNA Hata et al. (1996); Mukai et al. (1997)c; Skrincosky et al. (2000); Glosson et al. (2010) Glosson et al. (2010)d
HSV-1 (HHV-1) Herpes simplex virus type 1 (human herpesvirus 1) Herpesviridae Simplexvirus dsDNA Keller et al. (1970)c; Spear and Roizman (1970)c; Honess and Roizman (1975)c; Eisenberg et al. (1979); Wenske et al. (1982); Cohen et al. (1983); Respess et al. (1984); Serafini-Cessi et al. (1984) Keller et al. (1970)c; Olofsson et al. (1981); Serafini-Cessi, Dall’Olio, Scannavini, Costanzo et al. (1983); Olofsson et al. (1983); Dall’Olio et al. (1985); Lundstrom et al. (1987); Serafini-Cessi et al. (1988); Peng et al. (1998); Norberg et al. (2007)c; Bagdonaite et al. (2015); Norden et al. (2015) Kuhn et al. (1988); Teuton and Brandt (2007); Wang et al. (2009); Altgarde et al. (2015) Knowles and Person (1976); Campadelli-Fiume et al. (1982); Serafini-Cessi, Dall’Olio, Scannavini, Campadelli-Fiume et al. (1983) Olofsson and Lycke (1980); Norrild and Pedersen (1982); Serafini-Cessi, Dall’Olio, Scannavini, Campadelli-Fiume et al. (1983); Altgarde et al. (2015) Sodora et al. (1989)
HSV-2 (HHV-2) Herpes simplex virus type 2 (human herpesvirus 2) Herpesviridae Simplexvirus dsDNA Cohen et al. (1983); Zezulak and Spear (1983); Serafini-Cessi et al. (1985) Zezulak and Spear (1983); Serafini-Cessi et al. (1985); Serafini-Cessi et al. (1988); Iversen et al. (2016) Luo et al. (2015) Luo et al. (2015) Luo et al. (2015) Clo et al. (2012); Iversen et al. (2016)
VZV (HHV-3) Varicella-zoster virus (human herpesvirus 3) Herpesviridae Varicellovirus dsDNA Friedrichs and Grose (1984); Montalvo et al. (1985); Montalvo and Grose (1986); Montalvo and Grose (1987); Yao et al. (1993); Maresova et al. (2000); Yamagishi et al. (2008) Montalvo et al. (1985); Montalvo and Grose (1987); Yao et al. (1993); Bagdonaite et al. (2016) Suenaga et al. (2015) Montalvo et al. (1985)
FLUAV Influenza A virus Orthomyxoviridae Influenzavirus A (−)ssRNA Schwarz et al. (1977)c; Edwardson (1984); Blake et al. (2009); An et al. (2015) Stansell et al. (2015) Park et al. (2016); Wu et al. (2017) Edwardson (1984); Wu et al. (2017) Skehel et al. (1984); Yang et al. (2011); Wu et al. (2017)
HeV Hendra virus Paramyxoviridae Henipavirus (−)ssRNA Bowden et al. (2010); Colgrave et al. (2012) Colgrave et al. (2012) Bradel-Tretheway et al. (2015); Stone et al. (2016) Bradel-Tretheway et al. (2015); Stone et al. (2016) Bradel-Tretheway et al. (2015); Stone et al. (2016) Bradel-Tretheway et al. (2015) Bradel-Tretheway et al. (2015); Stone et al. (2016)
NiV Nipah virus Paramyxoviridae Henipavirus (−)ssRNA Bowden et al. (2008) Stone et al. (2016) Bradel-Tretheway et al. (2015); Stone et al. (2016) Aguilar et al. (2006); Garner et al. (2015) Stone et al. (2016)
MeV Measles virus Paramyxoviridae Morbillivirus (−)ssRNA Hu et al. (1995) Hu et al. (1995)
HRSV Human respiratory syncitial virus Paramyxoviridae Pneumovirus (−)ssRNA Lambert and Pons (1983); Gruber and Levine (1985) Gruber and Levine (1985)c Lambert and Pons (1983) Lambert and Pons (1983)
MuV Mumps virus Paramyxoviridae Rubulavirus (−)ssRNA Herrler and Compans (1983) Herrler and Compans (1983)
VACV Vaccinia virus Poxviridae Orthopoxvirus dsDNA Shida and Dales (1981) Shida and Dales (1981) Shida and Dales (1981)
HIV-1 Human immunodeficiency virus 1 Retroviridae Lentivirus ssRNA-RT Bernstein et al. (1994); Doores, Bonomelli et al. (2010); Bonomelli et al. (2011); Pabst et al. (2012); Go et al. (2013); Yang W et al. (2014); AlSalmi et al. (2015); Pritchard, Harvey et al. (2015); Behrens et al. (2016); Panico et al. (2016); Cao et al. (2017); Go et al. (2017); Struwe et al. (2017) Bernstein et al. (1994); Go et al. (2013); Yang Z et al. (2014); Stansell et al. (2015) Nakayama et al. (1998); Pollakis et al. (2001); Hong et al. (2002); Lin et al. (2003); Francois and Balzarini (2011); Zou et al. (2011); Wang et al. (2013); Mathys and Balzarini (2014); Lombardi et al. (2015); Mathys and Balzarini (2015); Termini et al. (2017) Mathys and Balzarini (2014); Mathys and Balzarini (2015) Mathys and Balzarini (2014); Mathys and Balzarini (2015) Sanders et al. (2002); Wei et al. (2003); Wang et al. (2013); Doores and Burton (2010); St-Pierre et al. (2011); van Montfort et al. (2011); Pritchard, Spencer et al. (2015); Behrens et al. (2016); Lee et al. (2016)
CHIKV Chikungunya virus Togaviridae Alphavirus (+)ssRNA Lancaster et al. (2016)
RRV Ross River virus Togaviridae Alphavirus (+)ssRNA Nelson et al. (2016)
SFV Semliki Forest virus Togaviridae Alphavirus (+)ssRNA Pesonen (1979); Rasilo and Renkonen (1979)
SINV Sindbis virus Togaviridae Alphavirus (+)ssRNA Sefton (1975)c; Burke and Keegstra (1979); Hsieh et al. (1983) Mann et al. (1983) Leavitt et al. (1977); Datema et al. (1984)
RUBV Rubella virus Togaviridae Rubivirus (+)ssRNA Ho-Terry and Cohen (1984); Hobman et al. (1991); Lundstrom et al. (1991) Ho-Terry and Cohen (1984)c; Lundstrom et al. (1991) Ho-Terry and Cohen (1984) Hobman et al. (1991)
aLiterature references are indicated as first author last name and year.
bNonhuman infecting virus historically used as model for investigating betacoronaviruses.
cIndirect evidence.
dOther functions.