Neuroligin 2 controls the maturation of GABAergic synapses and information processing in the retina.

In the present study, we investigated the role of Neuroligin 2 (NL2) in synaptic transmission and network function using the mouse retina as a model circuit. We show that NL2 is preferentially located at GABAergic rather than glycinergic or glutamatergic postsynapses. The absence of NL2 from the retina resulted in a severe reduction of GABA(A) receptor clustering, and in subtle alterations of the retinal circuitry. Light processing was impaired accordingly, and retinal ganglion cells, the output neurons of the retina, showed increased basal activity and altered coding of visual information. Together, our data indicate that NL2 is essential for the functional integrity of GABAergic signaling and as a consequence, for information processing in the retina.

West Nile virus infection induces interferon signalling in human retinal pigment epithelial cells.

PURPOSE: In addition to neuroinvasive disease, West Nile virus (WNV) infection is frequently associated with self-limiting chorioretinitis and vitritis. However, the mechanisms of ophthalmic WNV infection are rarely investigated, in part because of the lack of reliable in vitro models. The authors therefore established the first model of ocular WNV infection and investigated interaction of WNV with IFN signal-transduction mechanisms. METHODS: Human retinal pigment epithelial (RPE) cells were infected with WNV strain NY385-99 at a multiplicity of infection of 5. Virus replication was evaluated by virus titers at different times after infection. The susceptibility of RPE cells to WNV infection was confirmed by transmission electron microscopy. IFN-beta expression was assessed by quantitative real-time PCR and by measurements of antiviral activity in cell culture supernatants. IFN signaling was evaluated by phosphorylation of transducer and activator of transcription 1 and 2 (STAT1/2) proteins, with immunoblot analysis. RESULTS: RPE cells appeared to be highly sensitive to WNV infection. Maximum viral titers were found 24 hours after infection, followed by a continuous decline during the course of infection. WNV infection of RPE cells was followed by increased IFN-beta expression associated with IFN signaling and subsequent inhibition of WNV replication. CONCLUSIONS: In this study, the first cell culture model of ophthalmic WNV infection was developed and characterized in RPE cells, and the molecular mechanisms of WNV infection were studied. The data suggest that WNV induces a general antiviral state in RPE cells. This general antiviral state correlates with WNV-induced IFN signaling in retinal cells.

Anti-HIV, anti-poxvirus, and anti-SARS activity of a nontoxic, acidic plant extract from the Trifollium species Secomet-V/anti-vac suggests that it contains a novel broad-spectrum antiviral.

Enveloped animal viruses such as human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, human papillomavirus, Marburg, and influenza are major public health concerns around the world. The prohibitive cost of antiretroviral (ARV) drugs for most HIV-infected patients in sub-Saharan Africa and the serious side effects in those who have access to ARV drugs make a compelling case for the study of complementary and alternative therapies. Such therapies should have scientifically proved antiviral activity and minimal toxic effects. A plant extract, Secomet-V, with an anecdotal indication in humans for promise as an anti-HIV treatment, was investigated. Using a previously described attenuated vaccinia virus vGK5, we established the antiviral activity of Secomet-V. Chemical analysis showed that it has an acidic pH, nontoxic traces of iron (<10 ppm), and almost undetectable levels of arsenic (<1.0 ppm). The color varies from colorless to pale yellow to dark brown. The active agent is heat stable at least up to sterilizing temperature of 121 degrees C. The crude plant extract is a mixture of several small molecules separable by high-pressure liquid chromatography. The HIV viral loads were significantly reduced over several months in a few patients monitored after treatment with Secomet-V. Secomet-V was also found to have antiviral activity against the SARS virus but not against the West Nile virus. Secomet-V, therefore, is a broad-spectrum antiviral, which possibly works by neutralizing viral infectivity, resulting in the prevention of viral attachment.