Fetal-Maternal HLA-A and – B Discordance is Associated with Placental RNase Expression and Anti-HIV-1 Activity

Victoria   Ines   Bedoya; Fabian   Alberto   Jaimes; Julio   C.   Delgado; Claudia      Rugeles; Xiomara      Usuga; Wildeman      Zapata; Maria   Eugenia   Castano; Adriano      Boasso; Gene      Shearer; Maria   Teresa   Rugeles

Abstract

The incidence of maternal-to-fetal human immunodeficiency virus type 1 (HIV-1) transmission is 25-30% in absence of antiretroviral therapy, and is inversely associated with Human leukocyte antigens (HLA) class-I discordance. Based on our earlier report that mixed lymphocyte reactions (MLR) induce a ribonuclease (RNase) that inhibits HIV-1 replication, we proposed that maternal-fetal alloantigen stimulation activates factors that protect the fetus against vertically- transmitted infections. We investigate here whether the degree of mother-infant HLA discordance associates with the ability to produce anti-HIV-1 alloantigen-stimulated factor (ASF), and affects placental RNases. We also determine whether such HLA association is influenced by the mothers HIV-1 status. Paired maternal and cord blood leukocytes were tested for the induction of ASF by MLR, and typed for HLA-A and – B. The placentas were tested for mRNA expression of three RNases. Neonate anti-mother, but not mother anti-neonate MLR generated supernatants with anti-HIV-1 activity, that was associated with HLA class I discordance. This HLA association was not seen in the HIV-infected cohort. HLA class I discordance was also associated with expression of placental RNase 1. Our findings are consistent with the hypothesis that HLA class I discordance induces expression of RNases in the placenta that contribute to innate host resistance to HIV-1 and other viral infections.

Keywords: Anti-HIV-1 activity, RNases, HLA class-I discordance

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