Raltegravir blocks the infectivity of red-fluorescent-protein (mCherry)-labeled HIV-1 JR-FL in the setting of post-exposure prophylaxis in NOD/SCID/Jak3 −/− mice transplanted with human PBMCs

Hiromi Ogata-Aoki, Nobuyo Higashi-Kuwata, Shin ichiro Hattori, Hironori Hayashi, Matthew Danish, Manabu Aoki, Chiemi Shiotsu, Yumi Hashiguchi, Akinobu Hamada, Hisataka Kobayashi, Hironobu Ihn, Seiji Okada, Hiroaki Mitsuya

Research output: Contribution to journalArticlepeer-review

Abstract

Employing NOD/SCID/Jak3 −/− mice transplanted with human PBMCs (hNOJ mice) and replication-competent, red-fluorescent-protein (mCherry; mC)-labeled HIV-1 JR-FL (HIV mC ), we examined whether early antiretroviral treatment blocked the establishment of HIV-1 infection. The use of hNOJ mice and HIV mC enabled us to visually locate infection foci and to examine the early dynamics of HIV mC infection without using a large amount of antiretroviral unlike in non-human primate models. Although when raltegravir (RAL) administration was begun 1 day after intraperitoneal (ip) inoculation of HIV mC , no plasma p24 or plasma HIV-1-RNA (pRNA) were detected in 10 of 12 hNOJ (hNOJ mC RAL+ ) mice as assessed on the last day of the 14-day continuous twice-daily RAL administration, all 10 untreated hNOJ mC (hNOJ mC RAL− ) mice became positive for p24 and pRNA and had significantly swollen lymph nodes in peritoneal cavity and abundant p24 + /mC + /CD3 + /CD4 + T cells and p24 + /mC + /CD68 + monocytes/macrophages were identified in their omenta and mesenteric lymphoid tissues/lymph nodes upon necropsy of the mice on day 14. In 12 hNOJ mC RAL+ mice, no significantly swollen lymph nodes were seen compared to hNOJ mC RAL− mice; however, in the omentum of the 2 hNOJ mC RAL+ mice that were positive for pRNA and in site RNA, mC + /p24 + /CD3 + /CD83 + cells were identified, suggesting that viral breakthrough occurred later in the observation period. The present data suggest that the use of hNOJ mouse model and HIV mC may shed light on the study of early-phase dynamics of HIV-1 infection and cellular events in post-exposure/pre-exposure prophylaxis.

Original languageEnglish
Pages (from-to)78-88
Number of pages11
JournalAntiviral Research
Volume149
DOIs
Publication statusPublished - 2018 Jan
Externally publishedYes

Keywords

  • HIV-1 breakthrough
  • In vivo imaging
  • NOD/SCID/Jak3−/− (NOJ) mice
  • Post-exposure prophylaxis
  • Raltegravir administration
  • mCherry-labeled HIV-1 (HIVmC)

ASJC Scopus subject areas

  • Pharmacology
  • Virology

Fingerprint Dive into the research topics of 'Raltegravir blocks the infectivity of red-fluorescent-protein (mCherry)-labeled HIV-1 <sub>JR-FL</sub> in the setting of post-exposure prophylaxis in NOD/SCID/Jak3 <sup>−/−</sup> mice transplanted with human PBMCs'. Together they form a unique fingerprint.

Cite this