title: HIV-1 envelope replication and α4β7 utilization among newly infected subjects and their corresponding heterosexual partners.
abstract: BACKGROUND
  Previous studies suggest that active selection limits the number of HIV-1 variants acquired by a newly infected individual from the diverse variants circulating in the transmitting partner. We compared HIV-1 envelopes from 9 newly infected subjects and their linked transmitting partner to explore potential mechanisms for selection.
  
  
  RESULTS
  Recipient virus envelopes had significant genotypic differences compared to those present in the transmitting partner. Recombinant viruses incorporating pools of recipient and transmitter envelopes showed no significant difference in their sensitivity to receptor and fusion inhibitors, suggesting they had relatively similar entry capacity in the presence of low CD4 and CCR5 levels. Aggregate results in primary cells from up to 4 different blood or skin donors showed that viruses with envelopes from the transmitting partner as compared to recipient envelopes replicated more efficiently in CD4+ T cells, monocyte derived dendritic cell (MDDC) - CD4+ T cell co-cultures, Langerhans cells (LCs) - CD4+ T cell co-cultures and CD4+ T cells expressing high levels of the gut homing receptor, α4β7, and demonstrated greater binding to α4β7 high / CD8+ T cells. These transmitter versus recipient envelope virus phenotypic differences, however, were not always consistent among the primary cells from all the different blood or skin donation volunteers.
  
  
  CONCLUSIONS
  Although genotypically unique variants are present in newly infected individuals compared to the diverse swarm circulating in the chronically infected transmitting partner, replication in potential early target cells and receptor utilization either do not completely dictate this genetic selection, or these potential transmission phenotypes are lost very soon after HIV-1 acquisition.
authors.forename: Victor
authors.initials: V
authors.lastname: Pena-Cruz
authors.forename: Behzad
authors.initials: B
authors.lastname: Etemad
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Chatziandreou
authors.forename: Phyu Hninn
authors.initials: PH
authors.lastname: Nyein
authors.forename: Shannon
authors.initials: S
authors.lastname: Stock
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Reynolds
authors.forename: Oliver
authors.initials: O
authors.lastname: Laeyendecker
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Gray
authors.forename: David
authors.initials: D
authors.lastname: Serwadda
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Boston University, Boston, MA, USA. msagar@bu.edu.
authors.forename: Manish
authors.initials: M
authors.lastname: Sagar
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000821:virology; D002478:Cells, Cultured; D018920:Coculture Techniques; D015331:Cohort Studies; D003713:Dendritic Cells / Q000821:virology; D005191:Family Characteristics; D005260:Female; D015658:HIV Infections / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D020010:Heterosexuality; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008264:Macrophages / Q000821:virology; D008297:Male; D015728:Receptors, HIV / Q000378:metabolism; D012641:Selection, Genetic; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: D016023:Integrins; D015728:Receptors, HIV; D054299:env Gene Products, Human Immunodeficiency Virus; C071777:integrin alpha4beta7