The extracellular matrix molecule tenascin-C (TNC) is induced at the site of injury induced by infection with bacteria or virus. However, during chronic inflammation, TNC plays a detrimental role by promoting disease progression through multiple mechanisms. The role of TNC in HIV-1 infection was recently investigated. Some authors found significantly increased levels of TNC in the plasma of HIV-infected individuals. Others proposed that TNC, present in breast milk, participate in the inhibition of virus transmission during breath feeding.  Indeed, they found that TNC binds to the HIV envelope, thereby limiting HIV replication. However, the exact role of TNC in HIV-1 infection and its effect on primary cell activation, infection and inflammation are unknown.
 
To characterize the different roles of TNC on HIV-1 infection in more detail, we analyzed the levels of TNC in serum from HIV infected patients and determined a potential interaction of TNC with the HIV envelope protein by ELISA. TNC inhibition of viral replication was examined by a neutralization assay. An impact of TNC on T cell activation and HIV replication was measured by flow cytometry.
 
We found a lower concentration of TNC in sera from different HIV-1 infected cohorts compared to uninfected volunteers. Moreover, in primary T cells, TNC increased cell activation (with augmentation of CD25 and CD69 markers) and viral replication. However, we could not observe a direct binding of TNC to the HIV envelope protein in our experimental conditions.
 
These results support an involvement of TNC in HIV infection. Further studies are needed to characterize the multiple roles of TNC in HIV infection, in particular how HIV infection leads to TNC induction, which isoforms are expressed and how then TNC impacts viral activation and replication under physiological conditions.