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

• Published in: Antiviral research Vol. 149; p. 78
• Main Authors: Ogata-Aoki, Hiromi, Higashi-Kuwata, Nobuyo, Hattori, Shin-Ichiro, Hayashi, Hironori, Danish, Matthew, Aoki, Manabu, Shiotsu, Chiemi, Hashiguchi, Yumi, Hamada, Akinobu, Kobayashi, Hisataka, Ihn, Hironobu, Okada, Seiji, Mitsuya, Hiroaki
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2018
• Subjects: Animals; Anti-HIV Agents - pharmacology; Disease Models, Animal; Gene Expression; Genes, Reporter; Genetic Vectors - genetics; HIV Infections - drug therapy; HIV Infections - prevention & control; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - genetics; Humans; Immunohistochemistry; Janus Kinase 3 - deficiency; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - virology; Luminescent Proteins - genetics; Mice; Mice, Inbred NOD; Mice, Knockout; Mice, SCID; Post-Exposure Prophylaxis - methods; Raltegravir Potassium - pharmacology; Red Fluorescent Protein; Viral Load; NOD/SCID/Jak3−/− (NOJ) mice; Raltegravir administration; Post-exposure prophylaxis; HIV-1 breakthrough; In vivo imaging; mCherry-labeled HIV-1 (HIVmC)
• ISSN: 1872-9096
• DOI: 10.1016/j.antiviral.2017.09.003

Employing NOD/SCID/Jak3 mice transplanted with human PBMCs (hNOJ mice) and replication-competent, red-fluorescent-protein (mCherry; mC)-labeled HIV-1 (HIV ), we examined whether early antiretroviral treatment blocked the establishment of HIV-1 infection. The use of hNOJ mice and HIV enabled us to visually locate infection foci and to examine the early dynamics of HIV 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 , no plasma p24 or plasma HIV-1-RNA (pRNA) were detected in 10 of 12 hNOJ (hNOJ ) mice as assessed on the last day of the 14-day continuous twice-daily RAL administration, all 10 untreated hNOJ (hNOJ ) 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 mice, no significantly swollen lymph nodes were seen compared to hNOJ mice; however, in the omentum of the 2 hNOJ 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 may shed light on the study of early-phase dynamics of HIV-1 infection and cellular events in post-exposure/pre-exposure prophylaxis.