Unconventional secretion of viral proteins

Although largely less numerous and characterized than bacterial secreted effectors, several viral virulence factors are secreted by virus infected cells. However, their mode of secretion only starts to be studied at the molecular level. Several of these viral effectors are secreted using an unconventional secretion pathway, i.e. despite the lack of signal sequence. We here review recent results illustrating the diversity of these pathways. In the case of HIV-1 proteins Tat and matrix (p17) proteins, secretion directly takes place at the plasma membrane level following binding to PI(4,5)P₂. The secretion of HTLV-I Tax was found to partly rely on exocytic pathway intermediates. The secretion pathways of VP22 of Herpes simplex virus type I and VP40 of the Ebola virus are less well characterized but VP40 can be recruited to the plasma membrane by PI(4,5)P₂ that thus appears as a key partner enabling the unconventional secretion of many viral proteins. Several studies indicated that circulating retroviral transactivating proteins Tat and Tax are involved in the development of AIDS and HTLV-I associated myelopathy/tropical spastic paraparesis, respectively.