Mouse Anti-Human CD151 Hybridoma [61-7]

Tetraspanins are suggested to regulate the composition of cell membrane components and control intracellular transport, which leaves them vulnerable to utilization by pathogens such as human papillomaviruses (HPV) and cytomegaloviruses (HCMV) to facilitate host cell entry and subsequent infection. In this study, by means of cellular depletion, the cluster of differentiation (CD) tetraspanins CD9, CD63, and CD151 were found to reduce HPV16 infection in HeLa cells by 50 to 80%. Moreover, we tested recombinant proteins or peptides of specific tetraspanin domains on their effect on the most oncogenic HPV type, HPV16, and HCMV. We found that the C-terminal tails of CD63 and CD151 significantly inhibited infections of both HPV16 and HCMV. Although CD9 was newly identified as a key cellular factor for HPV16 infection, the recombinant CD9 C-terminal peptide had no effect on infection. Based on the determined half-maximal inhibitory concentration (IC50), we classified CD63 and CD151 C-terminal peptides as moderate to potent inhibitors of HPV16 infection in HeLa and HaCaT cells, and in EA.hy926, HFF (human foreskin fibroblast) cells, and HEC-LTT (human endothelial cell-large T antigen and telomerase) cells for HCMV, respectively. These results indicate that HPV16 and HCMV share similar cellular requirements for their entry into host cells and reveal the necessity of the cytoplasmic CD151 and CD63 C-termini in virus infections. Furthermore, this highlights the suitability of these peptides for functional investigation of tetraspanin domains and as inhibitors of pathogen infections.

Background: This study was designed to determine the role of CD151 in platelet thrombus formation in vivo and define the contribution of platelet vs. endothelial CD151 in regulating platelet thrombus formation in vivo. Methods and Results: Using intravital microscopy and ferric chloride (FeCl3) injury of mesenteric arterioles, we found that thrombi formed in CD151+/- and CD151-/- mice were smaller and less stable, than those formed in CD151+/+ mice, with a tendency for embolization. Similarly, in Folt's FeCl3-induced carotid injury model, both CD151+/- and CD151-/- mice showed more prolonged times to 95% vessel occlusion than CD151+/+ mice. In addition, laser-induced injury of cremaster muscle arterioles showed that thrombi formed in CD151+/- and CD151-/- mice were smaller and less stable than those formed in CD151+/+ mice. Following platelet depletion/reconstitution with ex vivo-labeled donor platelets, platelet-depleted CD151+/+ mice that received reconstitution with CD151-/- platelets had smaller thrombi that were unstable and embolized. In contrast, platelet-depleted CD151-/- mice that received reconstitution with CD151+/+ platelets had normal thrombi that were stable. Conclusions: These data provide evidence that platelet CD151 is required for regulating thrombus formation in vivo.