title: No SEVI-mediated enhancement of rectal HIV-1 transmission of HIV-1 in two humanized mouse cohorts.
abstract: Amyloid fibrils from semen-derived peptide (SEVI) enhance HIV-1 infectivity in vitro but the ability of SEVI to mediate enhancement of HIV infection in vivo has not been tested. In this study we used immunodeficient mice reconstituted with human immune systems to test for in vivo enhancement of HIV-1 transmission. This mouse model supports mucosal transmission of HIV-1 via the intrarectal route leading to productive infection. In separate experiments with humanized mouse cohorts reconstituted with two different donor immune systems, high dose HIV-1JR-CSF that had been incubated with SEVI amyloid fibrils at physiologically relevant concentrations did not show an increased incidence of infection compared to controls. In addition, SEVI failed to enhance rectal transmission with a reduced concentration of HIV-1. Although we confirmed potent SEVI-mediated enhancement of HIV infectivity in vitro, this model showed no evidence that it plays a role in the much more complex situation of in vivo transmission.
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT 59840, USA.
authors.forename: Erik S
authors.initials: ES
authors.lastname: Van Dis
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT 59840, USA.
authors.forename: Tyler C
authors.initials: TC
authors.lastname: Moore
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT 59840, USA.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Lavender
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT 59840, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Messer
authors.affiliation: Institute of Medical Virology, National Reference Center for Retroviruses, University of Frankfurt, Frankfurt, Germany.
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Keppler
authors.affiliation: Institute for Virology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Verheyen
authors.affiliation: Institute for Virology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Dittmer
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT 59840, USA. Electronic address: khasenkrug@nih.gov.
authors.forename: Kim J
authors.initials: KJ
authors.lastname: Hasenkrug
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D015658:HIV Infections / Q000635:transmission*; D006801:Humans; D015994:Incidence; D008297:Male; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D012007:Rectum / Q000821:virology*; D012661:Semen / Q000737:chemistry*
chemical_list: D000682:Amyloid
keywords: Amyloid; HIV; Humanized mice; SEVI; Semen-derived enhancer of viral infection; Transmission