Phosphorylation of the HTLV-1 matrix L-domain-containing protein by virus-associated ERK-2 kinase

Abstract

L-domain-containing proteins from animal retroviruses play a critical role in the recruitment of the host cell endocytic machinery that is required for retroviruses budding. We recently demonstrated that phosphorylation of the p6 gag protein containing the L-domain of the human immunodeficiency virus type 1 regulates viral assembly and budding. Here, we investigated whether or not the L-domain-containing protein from another human retrovirus, namely the matrix protein of the human T-cell leukemia virus type 1, that contains the canonical PTAP and PPPY L-domain motifs, shares similar functional properties. We found that MA is phosphorylated at several sites. We identified one phosphorylated amino acid in the HTLV-1 MA protein as being S105, located in the close vicinity to the L-domain sequence. S105 phosphorylation was found to be mediated by the cellular kinase ERK-2 that is incorporated within HTLV-1 virus particles in an active form. Mutation of the ERK-2 target S105 residue into an alanine was found to decrease viral release and budding efficiency of the HTLV-1 ACH molecular clone from transfected cells. Our data thus support the postulate that phosphorylation of retroviral L-domain proteins is a common feature to retroviruses that participates in the regulation of viral budding.