HIV AND HCV INFECTION OF THE BRAIN IN HUMANIZED MICE

Purpose: In this study, we wished to determine the possibility of HIV and HCV infections in the brains of these mice in preparation of using the mice to study HIV and HCV co-infection of the brain and the roles of the co-infection in HIV/HCV-associated neurological diseases . Methods: Human CD34+ human hematopoietic stem cells (HSC) and hepatocyte progenitors were co-transplanted into the Balb/CRag2-/-𝛄C-null mice, which led to efficient engraftment of human leukocytes and hepatocytes. These humanized mice were infected with HCV alone or HCV and HIV. Two months after infection, livers and brains of these mice were collected. Half of the brain was fixed and paraffin-embedded for immunostaining for HIV p24 and HCV core; the other half of the brain was used for DNA and RNA extraction. Polymerase Chain Reaction (PCR) was performed to detect HIV DNA; Strand-specific Reverse Transcription Polymerase Chain Reaction (RT-PCR) was performed to detect positive-strand and negative strand HCV RNA. Results: Three of four mice in HCV mono-infected group, one of five mouse in the HCV/HIV co-infected group showed severe fibrosis in liver. The HCV core protein and HIV P24 protein were detected in the brain, although faint. All 5 mouse infected with HIV were detected for HIV DNA in the brain. All 4 HCV mono-infected mice and all 5 HCV/HIV co-infected mice were detected for positive-strand HCV RNA in their brains, while only 3 of those brains were detected for negative-strand HCV RNA. Conclusions: These results showed that HCV and HIV are both capable of gaining access into the brain and replicating in the brain of these mice and suggest that humanized mice could be used to study the effects of HCV infection and HCV/HIV co-infection on the brain dysfunction.