A group from Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, France, etc. has reported about structural and functional analysis of BK polyomavirus mutants regarding the infectivity.
https://pubmed.ncbi.nlm.nih.gov/36790933/
BK polyomavirus (BKPyV) is a small, non-enveloped, double-stranded DNA virus with an icosahedral capsid formed by 72 capsomers, where a capsomer is an association of a pentamer of the VP1 protein. BKPyV is known to interact with the urothelium and kidney epithelium through the gangliosides GT1b and GD1b, but also via other b-series gangliosides characterized by their α2-8-linked-disialyl moieties attached to the first galactose from the reducing end. BKPyV is an opportunistic virus with a prevalence of 80% in the worldwide population. Usually, infections occur asymptomatically during childhood and then lead to latency or persistence in the kidneys.
In this study, four variant forms of the VP1 protein were discussed. These variants had accumulated multiple mutations in the BC loop region of the VP1 protein, which is involved in the direct interaction of the virus with sialic acids. Those variants contained double mutant K69N E82Q (N-Q), E73Q mutant, E73A mutant, and triple mutant A72V E73Q E82Q (VQQ). Cell lines 293TT and RS were used to test the infectivity of all variant pseudoviruses as well as wild-type (WT) subtype Ib2 pseudovirus. Both cell lines were shown to contain monosialylated GM2 and GM3 a-series gangliosides along with neutral globosides from the structural studies using MS. In addition, RS cells specifically expressed b-series disialylated gangliosides GD2 and GD3 carrying α2-8-linked-disialyl epitopes.
The followings were found.
The N-Q variant lost all ganglioside-binding activity but retained infectivity in 293TT cells through a sialic acid-independent pathway, whereas VQQ showed enhanced ganglioside binding but almost completely lost infectivity in 293TT cells. One plausible explanation of these observations is that the VQQ variant may have lost the ability to interact with the unknown entry receptor employed by the N-Q variant to infect 293TT cells, and that this interaction is required, in addition to sialic acid binding, for infectious entry.