XMRV, A New Human Pathogenic Retrovirus: Detection In Chronic Diseases

1. Picture of cell art Picture of cell under a microscope Daniel L. Peterson, MD Whittemore Peterson Institute XMRV, A New Human Pathogenic Retrovirus: Detection In Chronic Diseases Daniel L. Peterson, MD Whittemore Peterson Institute October 29th, 2009

2. A debilitating disorder of unknown etiology that is estimated to affect 17 million people worldwide CDC Criteria (Fakuda, 1994) Persistent or relapsing fatigue of 6 mo or longer in duration,generally with a distinct onset Other known medical conditions excluded by clinical diagnosis Patients have at least 4 of the following symptoms: Impaired memory or concentration Sore throat Tender cervical or axillary lymph nodes Muscle pain Multi-joint pain New headaches Un-refreshing sleep Post exertional malaise lasting > 24 hrs Chronic Fatigue Syndrome (CFS) Persistent or relapsing fatigue of 6 mo or longer in duration, generally with a distinct onset Other known medical conditions excluded by clinical diagnosis Patients have at least 4 of the following symptoms: • Impaired memory or concentration • Sore throat • Tender cervical or axillary lymph nodes • Muscle pain • Multi-joint pain • New headaches • Un-refreshing sleep • Post exertional malaise lasting > 24 hrs A debilitating disorder of unknown etiology that is estimated to affect 17 million people worldwide CDC Criteria (Fakuda, 1994)

3. CFS is a heterogeneous, multi-system disorder manifested by inflammatory sequelae including: antiviral enzyme (RNase L) dysfunction low natural killer (NK) cell numbers and function innate immune activation increased numbers of activated T cells increased production of inflammatory Could these patients’ immune cells be infected with XMRV? CFS Clinical Research Findings • CFS is a heterogeneous, multi-system disorder manifested by inflammatory sequelae including: • antiviral enzyme (RNase L) dysfunction • low natural killer (NK) cell numbers and function • innate immune activation • increased numbers of activated T cells • increased production of inflammatory cytokines/chemokines Could these patients’ immune cells be infected with XMRV?

4. Picture of Envelope proteins and core proteins XMRV is a simple retrovirus—it encodes only for structural proteins Retroviruses are NOT ubiquitous and NOT benign They are all associated with disease such as cancer and neurological disease There are three known human exogenous retroviruses: HIV, HTLV-1 (both complex retroviruses) and XMRV Budding XMRV from a cell Gamma (Type-C) retrovirus XMRV Envelope proteins gp70 p15E Core proteins p30 p15 p12 p10 Envelope proteins Core proteins Budding XMRV from a cell • XMRV is a simple retrovirus—it encodes only for structural proteins • Retroviruses are NOT ubiquitous and NOT benign • They are all associated with disease such as cancer and neurological disease • There are three known human exogenous retroviruses: • HIV, HTLV-1 (both complex retroviruses) and XMRV 4

5. The importance of this slide- in the normals 3.75% is 10 million Americans! This gel is representative gel- 11 of the 101 are shown Joy Das Gupta in the Silverman lab obtained full length sequence from 3 patient samples To explore the relationship between XMRV in prostate cancer and the on in CFS These results are representative of the 101 patients tested. They reflect the presence of virus (DNA PCR). Presence of XMRV Sequences in Human DNA 68/101 (67%) 12 /320 (3.75%) These results are representative of the 101 patients tested. They reflect the presence of virus (DNA PCR).