Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma

PLoS Pathog. 2018 Apr 19;14(4):e1006944. doi: 10.1371/journal.ppat.1006944. eCollection 2018 Apr.


Despite extensive genetic diversity of HIV-1 in chronic infection, a single or few maternal virus variants become the founders of an infant's infection. These transmitted/founder (T/F) variants are of particular interest, as a maternal or infant HIV vaccine should raise envelope (Env) specific IgG responses capable of blocking this group of viruses. However, the maternal or infant factors that contribute to selection of infant T/F viruses are not well understood. In this study, we amplified HIV-1 env genes by single genome amplification from 16 mother-infant transmitting pairs from the U.S. pre-antiretroviral era Women Infant Transmission Study (WITS). Infant T/F and representative maternal non-transmitted Env variants from plasma were identified and used to generate pseudoviruses for paired maternal plasma neutralization sensitivity analysis. Eighteen out of 21 (85%) infant T/F Env pseudoviruses were neutralization resistant to paired maternal plasma. Yet, all infant T/F viruses were neutralization sensitive to a panel of HIV-1 broadly neutralizing antibodies and variably sensitive to heterologous plasma neutralizing antibodies. Also, these infant T/F pseudoviruses were overall more neutralization resistant to paired maternal plasma in comparison to pseudoviruses from maternal non-transmitted variants (p = 0.012). Altogether, our findings suggest that autologous neutralization of circulating viruses by maternal plasma antibodies select for neutralization-resistant viruses that initiate peripartum transmission, raising the speculation that enhancement of this response at the end of pregnancy could further reduce infant HIV-1 infection risk.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Neutralizing / immunology*
  • Female
  • Genetic Variation
  • HIV Antibodies / immunology
  • HIV Infections / immunology
  • HIV Infections / transmission*
  • HIV Infections / virology
  • HIV-1 / genetics*
  • Humans
  • Infant
  • Infectious Disease Transmission, Vertical*
  • Neutralization Tests
  • Peripartum Period
  • Plasma / metabolism*
  • Pregnancy
  • Pregnancy Complications, Infectious / etiology*
  • Pregnancy Complications, Infectious / metabolism
  • env Gene Products, Human Immunodeficiency Virus / genetics
  • env Gene Products, Human Immunodeficiency Virus / immunology*


  • Antibodies, Neutralizing
  • HIV Antibodies
  • env Gene Products, Human Immunodeficiency Virus