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Type I interferons (IFN\u03b1\/\u03b2) are critical mediators of any anti-viral immune response and IFN\u03b2 has been implicated in the temporary control of lentiviral infection in the brain. Here we show that transgenic mice expressing HIV-1 envelope glycoprotein 120 in their central nervous system (HIVgp120tg) mount a transient IFN\u03b2 response and provide evidence that IFN\u03b2 confers neuronal protection against HIVgp120 toxicity. In cerebrocortical cell cultures, neuroprotection by IFN\u03b2 against gp120 toxicity is dependent on IFN\u03b1 receptor 1 (IFNAR1) and the \u03b2-chemokine CCL4, as IFNAR1 deficiency and neutralizing antibodies against CCL4, respectively, abolish the neuroprotective effects. We find<jats:italic>in vivo<\/jats:italic>that IFN\u03b2 mRNA is significantly increased in HIVgp120tg brains at 1.5, but not 3 or 6 months of age. However, a four-week intranasal IFN\u03b2 treatment of HIVgp120tg mice starting at 3.5 months of age increases expression of CCL4 and concomitantly protects neuronal dendrites and pre-synaptic terminals in cortex and hippocampus from gp120-induced damage. Moreover,<jats:italic>in vivo<\/jats:italic>and<jats:italic>in vitro<\/jats:italic>data suggests astrocytes are a major source of IFN\u03b2-induced CCL4. Altogether, our results suggest exogenous IFN\u03b2 as a neuroprotective factor that has potential to ameliorate<jats:italic>in vivo<\/jats:italic>HIVgp120-induced brain injury.<\/jats:p>","DOI":"10.1038\/srep46514","type":"journal-article","created":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T09:20:47Z","timestamp":1492680047000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["IFN\u03b2 Protects Neurons from Damage in a Murine Model of HIV-1 Associated Brain Injury"],"prefix":"10.1038","volume":"7","author":[{"given":"Victoria E.","family":"Thaney","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan M.","family":"O\u2019Neill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie M.","family":"Hoefer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricky","family":"Maung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana B.","family":"Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Kaul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,20]]},"reference":[{"key":"BFsrep46514_CR1","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.1212\/01.WNL.0000287431.88658.8b","volume":"69","author":"A Antinori","year":"2007","unstructured":"Antinori, A. et al. 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