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

5 years ago

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

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

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DOI: S0166354217302656