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

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.

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