The tetraspanin CD9 promotes CD46-dependent cellular infection by HHV-6A and impairs CD-46 independent infection by HHV-6B.
CD46 and CD134 are thought to be the main entry receptor for HHV-6A and HHV-6B, respectively, although there is evidence that some strains of HHV-6B can also use CD46.
Investigators from the laboratory of Per Hollsberg at Aarhus University in Denmark conducted a series of experiments with both HHV-6A/B in various cell lines to assess the roles of CD46 and CD134 in promoting infection by HHV-6A/B. Then, experiments were done to assess the possible modulating role of the tetaspanin CD9, with which CD46 is known to form complexes in the cell membrane.
In SupT1 cells, knockout of CD46 abolished binding and infection by both HHV-6A and -6B. In contrast, in Molt3 cells knockout of both CD46 and CD134 did not prevent infection by HHV-6B, suggesting that HHV-6B may be able to use one or more additional receptors to infect Molt3 cells.
As for the modulating role of CD9, knockout of CD9 in SupT1 cells did not prevent binding of either HHV-6A or -6B. However, knocking out CD9 considerably reduced the expression of several important immediate early (IE) transcripts, and reconstituting CD9 increased the expression of these IE transcripts. So, CD9 promoted CD46-dependent infection. In contrast, in Molt3 cells, knocking out CD9 promoted the infection by HHV-6B, indicating that CD9 impairs CD46-independent infection.
Thus, CD9 appears to have a modulating role in the ability of both HHV-6A and -6B to infect cells, but its modulating role is varies in different cell lines.
Read the full article: Schack 2021