HIV-1 TAT PROTEIN IMPAIRS HUMAN SPERM ACROSOME EXOCYTOSIS

PACHECO GUIÑAZÚ AB; VAQUER CINTIA; SUHAIMAN LAILA; LEONARDO PELLETÁN; BELMONTE SILVIA

Mar del Plata

Congreso; L1 Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular. SAIB.; 2015

Human immunodeficiency virus type 1 (HIV-1) transcription relies on its transactivating Tat protein. Although devoid of a signal sequence, Tat is released by infected cells. Secreted Tat can affect uninfected cells, thereby contributing to HIV-1 pathogenesis. Tat inhibits neurosecretion in PC12 cells and these cells actively internalize Tat by endocytosis. In this work, we focused on the role of Tat in human sperm acrosome secretion, a regulated calcium dependent exocytosis necessary for fertilization. Given that the spermatozoon is a non-endocytic cell, we first tested if the protein was able to penetrate intact cell membranes. We incubated sperm with recombinant WT Tat (using the physiological concentration present in HIV patients? serum) and combined biochemical, functional, and microscopy-based methods to show that WT Tat is capable to permeate intact sperm membranes. Further, by using exocytosis assays, we demonstrated that WT Tat inhibited progesterone-induced acrosome reaction. Additionally, we evaluated a variety of Tat mutants to elucidate the mechanisms involved in protein internalization and exocytosis inhibition. So far, the results obtained indicate that Tat is able to permeate through the sperm plasma membrane impairing the acrosomal exocytosis. Our data provide insights compelling the physiological role of Tat present in semen of HIV patients.