The spontaneous interaction between human papillomavirus type 16 (HPV16) L1 virus-like particles (VLPs) and non-functionalized gold nanoparticles (nfGNPs) interferes with the nfGNPs' salt-induced aggregation, inhibiting the red-blue color shift in the presence of NaCl. Electron microscopy and competition studies showed that color-shift inhibition is a consequence of direct nfGNP-VLP interaction and, thus, may produce a negative impact on the virus entry cell process. Here, an in vitro infection system based on the HPV16 pseudovirus (PsV) was used to stimulate the natural infection process in vitro. PsVs carry a pseudogenome with a reporter gene, resulting in a fluorescent signal when PsVs infect a cell, allowing quantification of the viral infection process. Aggregation assays showed that nfGNP-treated PsVs also inhibit color shift in the presence of NaCl. High-resolution microscopy confirmed nfGNP-PsV complex formation. In addition, PsVs can interact with silver nanoparticles, suggesting a generalized interaction of metallic nanoparticles with HPV16 capsids. The treatment of PsVs with nfGNPs produced viral infection inhibition at a higher level than heparin, the canonical inhibitor of HPV infection. Thus, nfGNPs can efficiently interfere with the HPV16 cell entry process and may represent a potential active component in prophylactic formulations to reduce the risk of HPV infection.
Keywords: HPV; gold nanoparticles; human papillomavirus; nanocomplex formation; nanoprophylaxis; pseudovirus; viral infection inhibition; viral inhibition.