Fetal-maternal HLA-A and -B discordance is associated with placental RNase expression and anti-HIV-1 activity.
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 mother's 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.
Bedoya
Victoria Inés
VI
Immunovirology, University of Antioquia, Medellín, Colombia. vibe@elhospital.org.co
Jaimes
Fabian Alberto
FA
Delgado
Julio C
JC
Rugeles
Claudia
C
Usuga
Xiomara
X
Zapata
Wildeman
W
Castaño
María Eugenia
ME
Boasso
Adriano
A
Shearer
Gene
G
Rugeles
María Teresa
MT
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D015234:HLA-A Antigens / Q000276:immunology / Q000378:metabolism; D015235:HLA-B Antigens / Q000276:immunology / Q000378:metabolism; D054502:Histocompatibility, Maternal-Fetal / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D007519:Isoantigens / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000821:virology; D012260:Ribonucleases / Q000378:metabolism* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D007519:Isoantigens; D012260:Ribonucleases