posted on 2021-03-09, 19:04authored byDesiree Schütz, Clarissa Read, Rüdiger Groß, Annika Röcker, Sascha Rode, Karthikeyan Annamalai, Marcus Fändrich, Jan Münch
Positively charged
naturally occurring or engineered peptide nanofibrils
(PNF) are effective enhancers of lentiviral and retroviral transduction,
an often rate-limiting step in gene transfer and gene therapy approaches.
These polycationic PNF are thought to bridge the electrostatic repulsions
between negatively charged membranes of virions and cells, thereby
enhancing virion attachment to and infection of target cells. Here,
we analyzed PNF, which are formed by the peptide AL1, that represents
a fragment of an immunoglobulin light chain that causes systemic AL
amyloidosis. We found that negatively charged AL1 PNF interact with
viral particles to a comparable extent as positively charged PNF.
However, AL1 PNF lacked cell-binding activity, and consequently, did
not enhance retroviral infection. These findings show that virion
capture and cell binding of PNF are mediated by different mechanisms,
offering avenues for the design of advanced PNF with selective functions.