Background. EcoHIV is a chimeric HIV that replicates in mice in CD4+ T cells, macrophages, and microglia (but not in neurons), causing lasting neurocognitive impairment resembling neurocognitive disease in people living with HIV. The present study was designed to develop EcoHIV-susceptible primary mouse brain cultures to investigate the indirect effects of HIV infection on neuronal integrity. Results. We used two EcoHIV clones encoding EGFP and mouse bone marrow-derived macrophages (BMM), mixed mouse brain cells, or enriched mouse glial cells from two wild-type mouse strains to test EcoHIV replication efficiency, the identity of productively infected cells, and neuronal apoptosis and integrity. EcoHIV replicated efficiently in BMM. In mixed brain cell cultures, EcoHIV targeted microglia but did not cause neuronal apoptosis. Instead, the productive infection of the microglia activated them and impaired synaptophysin expression, dendritic density, and axonal structure in the neurons. EcoHIV replication in the microglia and neuronal structural changes during infection were prevented by culture with an antiretroviral. Conclusions. In murine brain cell cultures, EcoHIV replication in the microglia is largely responsible for the aspects of neuronal dysfunction relevant to cognitive disease in infected mice and people living with HIV. These cultures provide a tool for further study of HIV neuropathogenesis and its control.

Prion diseases are infectious and fatal neurodegenerative diseases which require the cellular prion protein, PrP^C, for development of diseases. The current study shows that the PrP^C augments infectivity and plaque formation of a mouse endogenous retrovirus, MuLV. We have established four neuronal cell lines expressing mouse PrP^C, PrP^+/+; two express wild type PrP^C (MoPrP^wild) and the other two express mutant PrP^C (MoPrP^mut). Infection of neuronal cells from various PrP^+/+ and PrP^-/- (MoPrP^KO) lines with MuLV yielded at least three times as many plaques in PrP^+/+ than in PrP^-/-. Furthermore, among the four PrP^+/+ lines, one mutant line, P101L, had at least 2.5 times as many plaques as the other three PrP^+/+ lines. Plaques in P101L were four times larger than those in other PrP^+/+ lines. Colocalization of PrP and CAgag was seen in MuLV-infected PrP^+/+ cells. In the PrP-MuLV interaction, the involvement of galectin-3 and -6 was observed by immunoprecipitation with antibody to PrP^C. These results suggest that PrP^C combined with galectin-3 and -6 can act as a receptor for MuLV. P101L, the disease form of mutant PrP^C results suggest the genetic mutant form of PrP^C may be more susceptible to viral infection.