The central conserved region (CCR) of respiratory syncytial virus (RSV) G protein modulates host miRNA expression and alters the cellular response to infection

Respiratory Syncytial Virus (RSV) infects respiratory epithelial cells and deregulates host gene expression by many mechanisms including expression of RSV G protein (RSV G). RSV G protein encodes a central conserved region (CCR) containing a CX3C motif that functions as a fractalkine mimic. Disruption of the CX3C motif (a.a. 182–186) located in the CCR of the G protein has been shown to affect G protein function in vitro and the severity of RSV disease pathogenesis in vivo. We show that infection of polarized Calu3 respiratory cells with recombinant RSV having point mutations in Cys173 and 176 (C173/176S) (rA2-GC12), or Cys186 (C186S) (rA2-GC4) is associated with a decline in the integrity of polarized Calu-3 cultures and decreased virus production. This is accompanied with downregulation of miRNAs let-7f and miR-24 and upregulation of interferon lambda (IFNλ), a primary antiviral cytokine for RSV in rA2-GC12/rA2-GC4 infected cells. These results suggest that residues in the cysteine noose region of RSV G protein can modulate IFN λ expression accompanied by downregulation of miRNAs, and are important for RSV G protein function and targeting

Detection of Novel SARS-like and Other Coronaviruses in Bats from Kenya

Diverse coronaviruses have been identified in bats from several continents but not from Africa. We identified group 1 and 2 coronaviruses in bats in Kenya, including SARS-related coronaviruses. The sequence diversity suggests that bats are well-established reservoirs for and likely sources of coronaviruses for many species, including humans

Documentation of Fiji's endemic and introduced land snail fauna

This document is part of a technical report series on conservation projects funded by the Critical Ecosystem Partnership Fund (CEPF) and the Conservation International Pacific Islands Program (CI-Pacific). The main purpose of this series is to disseminate project findings and successes to a broader audience of conservation professionals in the Pacific, along with interested members of the public and students. The reports are being prepared on an ad-hoc basis as projects are completed and written up. In most cases the reports are composed of two parts, the first part is a detailed technical report on the project which gives details on the methodology used, the results and any recommendations. The second part is a brief project completion report written for the donor and focused on conservation impacts and lessons learned. The CEPF fund in the Polynesia-Micronesia region was launched in September 2008 and will be active until 2013. It is being managed as a partnership between CI Pacific and CEPF. The purpose of the fund is to engage and build the capacity of non-governmental organizations to achieve terrestrial biodiversity conservation. The total grant envelope is approximately US$6 million, and focuses on three main elements: the prevention, control and eradication of invasive species in key biodiversity areas (KBAs); strengthening the conservation status and management of a prioritized set of 60 KBAs and building the awareness and participation of local leaders and community members in the implementation of threatened species recovery plans. Since the launch of the fund, a number of calls for proposals have been completed for 14 eligible Pacific Island Countries and Territories (Samoa, Tonga, Kiribati, Fiji, Niue, Cook Islands, Palau, FSM, Marshall Islands, Tokelau Islands, French Polynesia, Wallis and Futuna, Eastern Island, Pitcairn and Tokelau). By late 2012 more than 90 projects in 13 countries and territories were being funded. The Polynesia-Micronesia Biodiversity Hotspot is one of the most threatened of Earth’s 34 biodiversity hotspots, with only 21 percent of the region’s original vegetation remaining in pristine condition.  The Hotspot faces a large number of severe threats including invasive species, alteration or destruction of native habitat and over exploitation of natural resources.  The limited land area exacerbates these threats and to date there have been more recorded bird extinctions in this Hotspot than any other.  In the future climate change is likely to become a major threat especially for low lying islands and atolls which could disappear completely

Neutralizing Anti-F Glycoprotein and Anti-Substance P Antibody Treatment Effectively Reduces Infection and Inflammation Associated with Respiratory Syncytial Virus Infection

Respiratory syncytial virus (RSV) is the most important virus mediating lower respiratory tract illness in infants and young children. RSV infection is associated with pulmonary inflammation and increased levels of substance P (SP), making the airways and leukocytes that express SP receptors susceptible to the proinflammatory effects of this peptide. This study examines combining neutralizing anti-F glycoprotein and anti-SP antibody treatment of RSV-infected BALB/c mice to inhibit RSV replication and inflammation associated with infection. BALB/c mice were prophylactically treated with antibody prior to RSV infection or were therapeutically treated at day 2 or 6 post-RSV infection. Prophylactic or therapeutic treatment with anti-SP antibodies promptly reduced pulmonary inflammatory cell infiltration and decreased the number of cells expressing proinflammatory cytokines, while anti-F antibody treatment reduced virus titers. The results suggest that combined anti-viral and anti-SP antibody treatment may be effective in treating RSV disease

Enhanced Disease and Pulmonary Eosinophilia Associated with Formalin-Inactivated Respiratory Syncytial Virus Vaccination Are Linked to G Glycoprotein CX3C-CX3CR1 Interaction and Expression of Substance P

Vaccination with formalin-inactivated respiratory syncytial virus (FI-RSV) vaccine or RSV G glycoprotein results in enhanced pulmonary disease after live RSV infection. Enhanced pulmonary disease is characterized by pulmonary eosinophilia and is associated with a substantial inflammatory response. We show that the absence of the G glycoprotein or G glycoprotein CX3C motif during FI-RSV vaccination or RSV challenge of FI-RSV-vaccinated mice, or treatment with anti-substance P or anti-CX3CR1 antibodies, reduces or eliminates enhanced pulmonary disease, modifies T-cell receptor Vβ usage, and alters CC and CXC chemokine expression. These data suggest that the G glycoprotein, and in particular the G glycoprotein CX3C motif, is key in the enhanced inflammatory response to FI-RSV vaccination, possibly through the induction of substance P

Combination therapy using monoclonal antibodies against respiratory syncytial virus (RSV) G glycoprotein protects from RSV disease in BALB/c mice.

Therapeutic options to control respiratory syncytial virus (RSV) are limited, thus development of new therapeutics is high priority. Previous studies with a monoclonal antibody (mAb) reactive to an epitope proximal to the central conserved region (CCR) of RSV G protein (mAb 131-2G) showed therapeutic efficacy for reducing pulmonary inflammation RSV infection in BALB/c mice. Here, we show a protective effect in RSV-infected mice therapeutically treated with a mAb (130-6D) reactive to an epitope within the CCR of G protein, while treatment with a mAb specific for a carboxyl G protein epitope had no effect. Combined treatment with mAbs 130-6D and 131-2G significantly decreased RSV-associated pulmonary inflammation compared to either antibody alone. The results suggest that anti-RSV G protein mAbs that react at or near the CCR and can block RSV G protein-mediated activities are effective at preventing RSV disease and may be an effective strategy for RSV therapeutic treatment

CD154 Blockade Results in Transient Reduction in Theiler's Murine Encephalomyelitis Virus-Induced Demyelinating Disease

Transient CD154 blockade at the onset of Theiler's murine encephalomyelitis virus-induced demyelinating disease ameliorated disease progression for 80 days, reduced immune cell infiltration, and transiently increased viral loads in the central nervous system. Peripheral antiviral and autoimmune T-cell responses were normal, and disease severity returned to control levels by day 120