title: Postnatally-transmitted HIV-1 Envelope variants have similar neutralization-sensitivity and function to that of nontransmitted breast milk variants.
abstract: BACKGROUND
  Breastfeeding is a leading cause of infant HIV-1 infection in the developing world, yet only a minority of infants exposed to HIV-1 via breastfeeding become infected. As a genetic bottleneck severely restricts the number of postnatally-transmitted variants, genetic or phenotypic properties of the virus Envelope (Env) could be important for the establishment of infant infection. We examined the efficiency of virologic functions required for initiation of infection in the gastrointestinal tract and the neutralization sensitivity of HIV-1 Env variants isolated from milk of three postnatally-transmitting mothers (n = 13 viruses), five clinically-matched nontransmitting mothers (n = 16 viruses), and seven postnatally-infected infants (n = 7 postnatally-transmitted/founder (T/F) viruses).
  
  
  RESULTS
  There was no difference in the efficiency of epithelial cell interactions between Env virus variants from the breast milk of transmitting and nontransmitting mothers. Moreover, there was similar efficiency of DC-mediated trans-infection, CCR5-usage, target cell fusion, and infectivity between HIV-1 Env-pseudoviruses from nontransmitting mothers and postnatal T/F viruses. Milk Env-pseudoviruses were generally sensitive to neutralization by autologous maternal plasma and resistant to breast milk neutralization. Infant T/F Env-pseudoviruses were equally sensitive to neutralization by broadly-neutralizing monoclonal and polyclonal antibodies as compared to nontransmitted breast milk Env variants.
  
  
  CONCLUSIONS
  Postnatally-T/F Env variants do not appear to possess a superior ability to interact with and cross a mucosal barrier or an exceptional resistance to neutralization that define their capability to initiate infection across the infant gastrointestinal tract in the setting of preexisting maternal antibodies.
authors.affiliation: Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Genevieve G
authors.initials: GG
authors.lastname: Fouda
authors.forename: Tatenda
authors.initials: T
authors.lastname: Mahlokozera
authors.forename: Jesus F
authors.initials: JF
authors.lastname: Salazar-Gonzalez
authors.forename: Maria G
authors.initials: MG
authors.lastname: Salazar
authors.forename: Gerald
authors.initials: G
authors.lastname: Learn
authors.forename: Surender B
authors.initials: SB
authors.lastname: Kumar
authors.forename: S Moses
authors.initials: SM
authors.lastname: Dennison
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Russell
authors.forename: Katherine
authors.initials: K
authors.lastname: Rizzolo
authors.forename: Frederick
authors.initials: F
authors.lastname: Jaeger
authors.forename: Fangping
authors.initials: F
authors.lastname: Cai
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Vandergrift
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Beatrice
authors.initials: B
authors.lastname: Hahn
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Christina
authors.initials: C
authors.lastname: Ochsenbauer
authors.forename: Ronald
authors.initials: R
authors.lastname: Swanstrom
authors.forename: Steve
authors.initials: S
authors.lastname: Meshnick
authors.forename: Victor
authors.initials: V
authors.lastname: Mwapasa
authors.forename: Linda
authors.initials: L
authors.lastname: Kalilani
authors.forename: Susan
authors.initials: S
authors.lastname: Fiscus
authors.forename: David
authors.initials: D
authors.lastname: Montefiori
authors.forename: Barton
authors.initials: B
authors.lastname: Haynes
authors.forename: Jesse
authors.initials: J
authors.lastname: Kwiek
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.forename: Sallie R
authors.initials: SR
authors.lastname: Permar
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood / Q000378:metabolism; D001942:Breast Feeding; D015331:Cohort Studies; D005260:Female; D041981:Gastrointestinal Tract / Q000276:immunology / Q000821:virology*; D015483:HIV Antibodies / Q000097:blood / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000635:transmission*; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008895:Milk, Human / Q000276:immunology* / Q000821:virology; D009500:Neutralization Tests; D010802:Phylogeny; D017423:Sequence Analysis, RNA; D019562:Viral Load; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus