Wednesday, May 18, 2011

2007 NIH $1M/yr retrovirus study expanded to include XMRV in 2010 "XMRV is a threat to the human genome"

by XMRV Global Action on Wednesday, May 18, 2011:

Project Number: 1ZIAMH002592-19
Contact Principal Investigator: EIDEN, MARIBETH V.

Fiscal Year: 2010 Award Notice Date:
Budget Start Date: not given
Budget End Date: not given
Administering Institutes or Centers: NATIONAL INSTITUTE OF MENTAL HEALTH
Project Funding Information for 2010: Total Funding: $1,538,297

(lp: my bolds and paragraphs)

The second focus of our section's research is based on determining whether gammaretroviral agents are etiologically liked to neurological disorders in humans. It has been reported that gammaretroviruses are present in the US population at a frequency that exceeds domestic HIV-1 infection rates.

The gammaretrovirus XMRV has been isolated from patients with prostate cancer and more recently with chronic fatigue syndrome (CFS) and in children diagnosed with neuroimmune disorders. The NIH has sponsored CFS research for many years and is committed to increasing both the amount and quality of research in this area. Through September 1999, the National Institute of Allergy and Infectious Diseases (NIAID) held sole responsibility for research in this area. In October 1999, Dr. Harold Varmus, in consultation with Dr. Anthony Fauci, recognizing that a multidisciplinary and integrated approach encompassing the missions of many NIH ICs was necessary to address CFS, incorporated responsibility into the Office of the Director (OD).

Our lab is recognized for our research on a similar gammaretrovirus isolated from nonhuman primates, gibbon ape leukemia virus (GALV). GALV is the only gammaretrovirus other than XMRV found in primates.

In collaboration with Frank Ruscetti at the NCI, Bill Switzer at the CDC and Suzan Winfield and Jessica Siegal-Willcot at the National Zoo, we are investigating the source animal for XMRV, and screening gibbon apes in US zoos for the presence of GALV and XMRV.

We have obtained samples from the CDC and the Biological Research Steering Committee that provide us with materials permitting us to determine that many gibbon apes at various zoos have been infected with an XMRV-like virus. We have determined the cell tropism of XMRV using an engineered biologically active XMRV virus with a GFP reporter gene and are identifying cellular factors that restrict XMRV infection of receptor bearing cells. These factors that can restrict XMRV infection will be used as a means of developing XMRV antiviral drugs.

In addition to being a horizontally transmitted infectious agent, XMRV is a threat to the human genome. We are in the process of isolating rat germ line cells and exposing these cells to engineered biologically active XMRV virus with a GFP reporter. Sperm obtained from these cells are being assessed. Positive results of sperm expressing GFP indicate that XMRV can be transmitted from infected individuals horizontally (i.e., to offspring as a mendelian trait) as well as vertically through the more traditionally route of viral infection. We used cysteine scanning mutagenesis (SCAM) methods to assess the topology of the GALV receptor and intend to identify extracellular domains of the XMRV receptor using similar methods. These studies will lead to the identification of the XMRV-binding domain. Finally the spread of most retroviruses is mediated not by direct virus infection but by cell-cell transmission from an infected cell to an uninfected cell. We have developed a model system to assess blocks to cell-cell virus transmission using spinning-disc confocal microscopy to visualized individual budding of fluorescently labeled virus particles into adjacent cells in three dimensional space over time.

Note: This project started being funded in 2007

They were looking at GALV (gibbon ape leukemia virus) and others as a model for emerging human viral diseases:

"Several viral diseases have emerged in the late 20th and early 21st centuries. This has created an urgent need to understand the mechanisms of viral entry underlying host range and pathogenicity, and a unique opportunity to exploit this knowledge to create new types of viral vectors that target therapeutic payloads to human cells with greater efficiency."

"A compelling question connected to differences in modes of virus entry between different retroviruses is what intracellular pathways and compartments viruses must be targeted to in order to achieve transport to a compartment in which reverse transcription can occur, and from which trafficking of the provirus to the nucleus can subsequently be achieved. In collaboration with Wayne Anderson (NCI) and Jon Marsh (NIMH) we have also determined that cell signaling through protein kinases regulates post-binding viral entry. Retroviruses isolated from primates, cats, and feral rodents have many common features including their association with a high incidence of leukemias/lymphomas in their hosts and their use of similar receptor proteins including a retrovirus recently isolated from koalas that is etiologically linked to lymphomas/leukemias in these marsupials"

Thanks to Jemal at the phoenix rising forum for the find & Joan WC for pointing it out.

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