Early events during BK virus entry and disassembly.

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• BK virus (BKV) establishes persistent infections but can reactivate in immunosuppressed individuals, causing diseases like polyomavirus nephropathy.
• The precise mechanisms of BKV entry and disassembly within host cells remain incompletely understood.

Purpose of the Study:

• To investigate the early events of BKV infection and disassembly in primary human renal proximal tubule epithelial (RPTE) cells.
• To elucidate the cellular components and processes involved in BKV entry and capsid protein modification.

Main Methods:

• Infection of primary human RPTE cells with BKV.
• Analysis of viral entry pathways, including pH dependence and microtubule transport.
• Investigation of endoplasmic reticulum (ER) involvement and protein trafficking.
• Examination of the major capsid protein VP1 structure and modifications.
• Assessing the role of Derlin-1 and proteasome function in BKV infection.

Main Results:

• BKV entry into RPTE cells requires an acidic environment and microtubule-dependent transport to the ER.
• VP1 undergoes pH- and ER-trafficking-dependent disulfide bond isomerization and cleavage.
• Derlin-1 interacts with VP1 and its inhibition, along with proteasome inhibition, disrupts BKV infection.
• These findings highlight the involvement of cellular machinery in BKV capsid rearrangement.

Conclusions:

• BKV entry and disassembly are complex, highly regulated processes dependent on cellular components.
• The ER and proteasome system play critical roles in early BKV infection stages.
• Understanding these mechanisms provides insights into BKV pathogenesis and potential therapeutic targets.