Bovine Papillomavirus Type 1: from Clathrin to Caveolin

Abstract

Viruses may infect cells through clathrin-dependent, caveolin-dependent, or clathrin-and caveolin-independent endocytosis. Bovine papillomavirus type 1 (BPV1) entry into cells has been shown to occur by clathrindependent endocytosis, a pathway that involves the formation of clathrin-coated pits and fusion to early endosomes. Recently, it has been demonstrated that the closely related JC virus can enter cells in clathrincoated vesicles and subsequently traffic to caveolae, the organelle where vesicles of the caveolin-dependent pathway deliver their cargo. In this study, we use immunofluorescence staining of BPV1 pseudovirions to show that BPV1 overlaps with the endosome marker EEA1 early during infection and later colocalizes with caveolin-1. We provide evidence through the colocalization of BPV1 with transferrin and cholera toxin B that BPVl trafficking may not be restricted to the clathrin-dependent pathway. Disrupting the entry of caveolar vesicles did not affect BPV1 infection; however, we show that blocking the caveolar pathway postentry results in a loss of BPV1 infection. These data indicate that BPV1 may enter by clathrin-mediated endocytosis and then utilize the caveolar pathway for infection, a pattern of trafficking that may explain the slow kinetics of BPV1 infection.

Role of Membrane Rafts in Viral Infection

“…The role of membrane rafts in entry of nonenveloped viruses has been investigated for simian virus 40 (SV40; Papovaviridae) [4][5][6][7][8][9][10][11][12], BK virus (Papovaviridae) [13][14][15], JC virus (Papovaviridae) [16], bovine papillomavirus (Papovaviridae) [17], human papillomavirus (HPV; Papovaviridae) [18][19][20][21][22][23][24][25][26], rotavirus (Reoviridae) [27][28][29], echovirus type 1 [30] and 11 (Picornaviridae) [31][32][33][34][35], enterovirus (Picornaviridae) [31], rhinovirus (Picornaviridae) [36], Coxsackievirus A9 and B4 (CAV; Picornaviridae) [37][38][39], and species C human adenovirus (HAdV; Adenoviridae) [40,41].…”

Replication and Assembly of Human Papillomaviruses

“…Postadsorption to the cell surface, internalization of virions has been shown to take many hours, and, depending on the papillomavirus type, virions can enter via clathrin-coated pits or caveolae (Fligge et al, 2001;Bousarghin et al, 2003;Day et al, 2003;Hindmarsh and Laimins, 2007;Smith et al, 2007). Recent studies involving entry pathways (e.g., clathrin-vs. caveolar-mediated endocytosis) and entry kinetics (e.g., few vs. many hours) of HPV have suffered due to a lack of consistency (Bousarghin et al, 2003;Culp and Christensen, 2004;Hindmarsh and Laimins, 2007;Smith et al, 2007;Laniosz et al, 2008). This may be due to the use of multiple types of synthetic papillomavirus particles and cell lines, in addition to the use of native virions, and cross-talk between clathrin and caveolar pathways (Fligge et al, 2001;Bousarghin et al, 2003;Hindmarsh and Laimins, 2007;Schelhaas et al, 2007;Laniosz et al, 2008).…”

“…This may be due to the use of multiple types of synthetic papillomavirus particles and cell lines, in addition to the use of native virions, and cross-talk between clathrin and caveolar pathways (Fligge et al, 2001;Bousarghin et al, 2003;Hindmarsh and Laimins, 2007;Schelhaas et al, 2007;Laniosz et al, 2008). Recent discoveries with polyomaviruses suggest that controversies over papillomavirus entry may be from the initial usage of clathrin-mediated endocytosis and later exploitation of caveolar endocytic machinery within the cell (Bousarghin et al, 2003;Querbes et al, 2006;Laniosz et al, 2008).…”

“…The L2/ genome complex may then interact with syntaxin 18, which ferries the complex to a perinuclear site (Bossis et al, 2005;Richards et al, 2006;Laniosz et al, 2008). L2 may then translocate the genome into the nucleus through its NLS (Fay et al, 2004;Bordeaux et al, 2006).…”

“…Recent studies involving entry pathways (e.g., clathrin-vs. caveolar-mediated endocytosis) and entry kinetics (e.g., few vs. many hours) of HPV have suffered due to a lack of consistency (Bousarghin et al, 2003;Culp and Christensen, 2004;Hindmarsh and Laimins, 2007;Smith et al, 2007;Laniosz et al, 2008). This may be due to the use of multiple types of synthetic papillomavirus particles and cell lines, in addition to the use of native virions, and cross-talk between clathrin and caveolar pathways (Fligge et al, 2001;Bousarghin et al, 2003;Hindmarsh and Laimins, 2007;Schelhaas et al, 2007;Laniosz et al, 2008). Recent discoveries with polyomaviruses suggest that controversies over papillomavirus entry may be from the initial usage of clathrin-mediated endocytosis and later exploitation of caveolar endocytic machinery within the cell (Bousarghin et al, 2003;Querbes et al, 2006;Laniosz et al, 2008).…”