Early events during BK virus entry and disassembly.
BK virus (BKV) is a nonenveloped, ubiquitous human polyomavirus that establishes a persistent infection in healthy individuals. It can be reactivated, however, in immunosuppressed patients and cause severe diseases, including polyomavirus nephropathy. The entry and disassembly mechanisms of BKV are not well defined. In this report, we characterized several early events during BKV infection in primary human renal proximal tubule epithelial (RPTE) cells, which are natural host cells for BKV. Our results demonstrate that BKV infection in RPTE cells involves an acidic environment relatively early during entry, followed by transport along the microtubule network to reach the endoplasmic reticulum (ER). A distinct disulfide bond isomerization and cleavage pattern of the major capsid protein VP1 was observed, which was also influenced by alterations in pH and disruption of trafficking to the ER. A dominant negative form of Derlin-1, an ER protein required for retro-translocation of certain misfolded proteins, inhibited BKV infection. Consistent with this, we detected an interaction between Derlin-1 and VP1. Finally, we show that proteasome function is also linked to BKV infection and capsid rearrangement. These results indicate that BKV early entry and disassembly are highly regulated processes involving multiple cellular components.
Jiang
Mengxi
M
Department of Microbiology and Immunology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109-5620, USA.
Abend
Johanna R
JR
Tsai
Billy
B
Imperiale
Michael J
MJ
D000643:Ammonium Chloride / Q000494:pharmacology; D001739:BK Virus / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology*; D001483:Base Sequence; D015153:Blotting, Western; D020126:Brefeldin A / Q000494:pharmacology; D002478:Cells, Cultured; D017931:DNA Primers; D004721:Endoplasmic Reticulum / Q000821:virology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000821:virology; D008561:Membrane Fusion; D008856:Microscopy, Fluorescence; D014779:Virus Replication
D017931:DNA Primers; D000643:Ammonium Chloride; D020126:Brefeldin A