Features of Maternal HIV-1 Associated with Lack of Vertical Transmission

Abstract

HIV-1 is transmitted from mother-to-child (vertical transmission) at an estimated rate of approximately 30% without any antiretroviral therapy (ART). However, administration of ART during pregnancy considerably diminishes the rate of mother-to-child transmission of HIV-1, which has become a standard of perinatal care in HIV-infected pregnant females in developed countries. Moreover, a majority of children born to HIV-infected mothers are uninfected without any ART. In addition, characteristics of HIV-1 and/or cellular factors in the mothers may play a role in influencing or preventing vertical transmission. Several studies, including from our laboratory have characterized the properties of HIV-1 from infected mothers that transmitted HIV-1 to their infants (transmitting mothers) and compared with those mothers that failed to transmit HIV-1 to their infants (non-transmitting mothers) in the absence of ART. One of the striking differences observed was that the non-transmitting mothers harbored a less heterogeneous HIV-1 population than transmitting mothers in the analyzed HIV-1 regions of p17gag,envV3,vifandvpr. The other significant and distinctive findings were that the functional domains of HIV-1vifandvprproteins were less conserved in non-transmitting mothers compared with transmitting mothers. Furthermore, there were differences seen in two important motifs of HIV-1 Gag p17, including conservation of QVSQNY motif and variation in KIEEEQN motif in non-transmitting mothers compared with transmitting mothers. Several of these distinguishing properties of HIV-1 in non-transmitting mothers provide insights in developing strategies for preventing HIV-1 vertical transmission.