Discussion
We recently reported that PsV of diverse PV types exhibited no selectivity in early events of infection at either mucosal or squamous epithelial sites, strongly implying that downstream post-entry events are responsible for the observed differences in PV tissue tropism (Handisurya et al., 2012). Specifically, we found that murine cutaneous and genital GW311616 hydrochloride were similarly permissive for PsV of multiple HPV types, including HPV16, MusPV1, and other animal PV. Despite this shared activity, we have shown in this study that HPV16 and MusPV1 appear to have evolved to interact with different host cell proteins. Although this difference in binding does not affect their intrinsic tropism, it could be an important consideration in interpreting the results of model systems based on heterologous species.
The HPV16-related data were important for our continued confidence that the mouse CVC model is a legitimate in vivo system for examining early events in HPV infection. The AlloDerm results also reaffirm our observations that the ECM secreted by HaCaT cells differs in its post-translational HSPG modifications from the ECM found on BM in vivo. As previously described, with HaCaT ECM, HPV16 does critically interact with HSPG, but the majority of the actual attachment is through laminin 332 (Cerqueira et al., 2013, Culp et al., 2006 and Selinka et al., 2007). As in vivo BM binding of HPV16 can be completely prevented with heparin or heparinase, laminin 332 does not apparently contribute in that context. In vitro experiments indicated that laminin 332 does not play a role in MusPV1 binding to HaCaT ECM (data not shown).
We recently reported that PsV of diverse PV types exhibited no selectivity in early events of infection at either mucosal or squamous epithelial sites, strongly implying that downstream post-entry events are responsible for the observed differences in PV tissue tropism (Handisurya et al., 2012). Specifically, we found that murine cutaneous and genital GW311616 hydrochloride were similarly permissive for PsV of multiple HPV types, including HPV16, MusPV1, and other animal PV. Despite this shared activity, we have shown in this study that HPV16 and MusPV1 appear to have evolved to interact with different host cell proteins. Although this difference in binding does not affect their intrinsic tropism, it could be an important consideration in interpreting the results of model systems based on heterologous species.
The HPV16-related data were important for our continued confidence that the mouse CVC model is a legitimate in vivo system for examining early events in HPV infection. The AlloDerm results also reaffirm our observations that the ECM secreted by HaCaT cells differs in its post-translational HSPG modifications from the ECM found on BM in vivo. As previously described, with HaCaT ECM, HPV16 does critically interact with HSPG, but the majority of the actual attachment is through laminin 332 (Cerqueira et al., 2013, Culp et al., 2006 and Selinka et al., 2007). As in vivo BM binding of HPV16 can be completely prevented with heparin or heparinase, laminin 332 does not apparently contribute in that context. In vitro experiments indicated that laminin 332 does not play a role in MusPV1 binding to HaCaT ECM (data not shown).