scholarly journals Evolution of Functional and Sequence Variants of the Mammalian XPR1 Receptor for Mouse Xenotropic Gammaretroviruses and the Human-Derived Retrovirus XMRV

2010 ◽  
Vol 84 (22) ◽  
pp. 11970-11980 ◽  
Author(s):  
Yuhe Yan ◽  
Qingping Liu ◽  
Kurt Wollenberg ◽  
Carrie Martin ◽  
Alicia Buckler-White ◽  
...  
Keyword(s):  
Virus Entry ◽  
Leukemia Virus ◽  
Laboratory Mouse ◽  
Wild Mouse ◽  
Chronic Fatigue ◽  
Receptor Function ◽  
Fatigue Syndrome ◽  
Novel Host ◽  
History Of ◽  
Leukemia Viruses

ABSTRACT Genetic conflicts between retroviruses and their receptors result in the evolution of novel host entry restrictions and novel virus envelopes, and such variants can influence trans-species transmission. We screened rodents and other mammals for sequence variation in the Xpr1 receptor for the mouse xenotropic or polytropic mouse leukemia viruses (X-MLVs or P-MLVs, respectively) of the gammaretrovirus family and for susceptibility to mouse-derived X/P-MLVs and to XMRV (xenotropic murine leukemia virus-related virus), an X-MLV-like virus isolated from humans with prostate cancer and chronic fatigue syndrome. We identified multiple distinct susceptibility phenotypes; these include the four known Xpr1 variants in Mus and a novel fifth Xpr1 gene found in Mus molossinus and Mus musculus. We describe the geographic and species distribution of the Mus Xpr1 variants but failed to find the X-MLV-restrictive laboratory mouse allele in any wild mouse. We used mutagenesis and phylogenetic analysis to evaluate the functional contributions made by constrained, variable, and deleted residues. Rodent Xpr1 is under positive selection, indicating a history of host-pathogen conflicts; several codons under selection have known roles in virus entry. All non-Mus mammals are susceptible to mouse X-MLVs, but some restrict other members of the X/P-MLV family, and the resistance of hamster and gerbil cells to XMRV indicates that XMRV has unique receptor requirements. We show that the hypervariable fourth extracellular XPR1 loop (ECL4) contains three evolutionarily constrained residues that do not contribute to receptor function, we identify two novel residues important for virus entry (I579 and T583), and we describe a unique pattern of ECL4 variation in the three virus-restrictive Xpr1 variants found in MLV-infected house mice; these mice carry different deletions in ECL4, suggesting either that these sites or loop size affects receptor function.

scholarly journals Rethinking childhood adversity in chronic fatigue syndrome

2015 ◽  
Author(s):  
James E Clark ◽  
Sean Davidson ◽  
Laura Maclachlan ◽  
Megan Lynn ◽  
Julia L Newton ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Childhood Trauma ◽  
Childhood Adversity ◽  
Chronic Fatigue ◽  
Childhood Trauma Questionnaire ◽  
History Of Childhood ◽  
Fatigue Syndrome ◽  
Increased Risk ◽  
Co Morbidity ◽  
History Of

Objectives: Previous studies have consistently shown increased rates of childhood adversity in chronic fatigue syndrome (CFS). However, such aetiopathogenic studies of CFS are potentially confounded by co-morbidity and misdiagnosis particularly with depression. We used a modelling approach with existing data and data generated in our examination of the rates of childhood adversity in a sample of CFS patients who had no lifetime history of depression. Methods: The childhood trauma questionnaire (CTQ) was completed by a sample of 52 participants and 19 controls with chronic fatigue syndrome who did not meet criteria for a psychiatric disorder (confirmed using the Structured Clinical Interview for DSM-IV). Subsequently, Mediation Analysis (Baye’s Rules) was used to establish the risk childhood adversity poses for CFS with and without depression. Results: In a cohort of CFS patients with depression robustly excluded, CTQ scores were markedly lower than in all previous studies and, in contrast to these previous studies, not increased compared with healthy controls. Post-hoc analysis showed that CTQ scores correlated with the number of depressive symptoms during the lifetime worst period of low mood. The probability of developing CFS given a history of childhood trauma was shown to be 4%, a two-fold increased risk compared to the general population. However, much of this risk is mediated by the concomitant development of major depression. Discussion: The data suggests that previous studies showing a relationship between childhood adversity and CFS may be mediated by depression

scholarly journals The tale of xenotropic murine leukemia virus-related virus

2012 ◽  
Vol 93 (5) ◽  
pp. 915-924 ◽  
Author(s):  
Harriet C. T. Groom ◽  
Kate N. Bishop
Keyword(s):  
Murine Leukemia Virus ◽  
Prostate Cancer Patient ◽  
Leukemia Virus ◽  
Chronic Fatigue ◽  
Xenotropic Murine Leukemia ◽  
Fatigue Syndrome ◽  
Related Virus ◽  
Potential Association ◽  
The Media ◽  
Murine Leukemia

In 2006, a new retrovirus was isolated from prostate cancer patient tissue. Named xenotropic murine leukemia virus-related virus (XMRV), this was potentially the third class of retrovirus to be pathogenic in humans. XMRV made a more dramatic impact on the wider scientific community, and indeed the media, in 2009 when it was reported to be present in a remarkably high proportion of patients with chronic fatigue syndrome as well as a significant, albeit smaller, proportion of healthy controls. The apparent strong link to disease and the fear of a previously unknown retrovirus circulating in the general population lead to a surge in XMRV research. Subsequent studies failed to find an association of XMRV with disease and, in most cases, failed to find the virus in human samples. In 2011, the case against XMRV and human disease strengthened, ending with several decisive publications revealing the origin of the virus and demonstrating contamination of samples. In this review, we outline the passage of research on XMRV and its potential association with disease from its isolation to the present day, where we find ourselves at the end of a turbulent story.

Mortality in a cohort of chronically fatigued patients

2006 ◽  
Vol 36 (9) ◽  
pp. 1301-1306 ◽  
Author(s):  
WAYNE R. SMITH ◽  
CAROLYN NOONAN ◽  
DEDRA BUCHWALD
Keyword(s):  
Tertiary Care ◽  
Chronic Fatigue ◽  
Care Clinic ◽  
Death Rates ◽  
Fatigue Syndrome ◽  
All Cause Mortality ◽  
Control And Prevention ◽  
Table Analysis ◽  
History Of ◽  
The Difference

Background. Comprehensive studies of mortality among patients with chronic fatigue (CF) and chronic fatigue syndrome (CFS) have not been published, but several sources suggest that CFS is associated with an elevated risk for suicide.Method. Data on 1201 chronically fatigued patients followed in a university-affiliated tertiary-care clinic for up to 14 years were submitted to the Center for Disease Control and Prevention (CDC) National Death Index (NDI) to evaluate all-cause and suicide-caused death rates against standardized mortality rates (SMRs). We used Life Table Analysis to examine the influence of sex and diagnoses of CFS and depression.Results. All-cause mortality in chronically fatigued patients was no higher than expected, but suicide-caused death rates were more than eight times higher than in the US general population. The significant elevation in the SMR of suicide was restricted to those who did not meet criteria for CFS [SMRCF=14·2, 95% confidence interval (CI) 5·7–29·3 versus SMRCFS=3·6, 95% CI 0·4–12·9]. Among chronically fatigued patients who did not meet CFS criteria, those with a lifetime history of major depression (MD) had higher suicide-caused death rates than among their non-depressed counterparts (SMRMD=19·1, 95% CI 7·0–41·5 versus SMRNMD=5·6, 95% CI 0·1–31·4), although the difference was not significant.Conclusions. CFS does not appear to be associated with increased all-cause mortality or suicide rates. Clinicians, however, should carefully evaluate patients with CF for depression and suicidality.

Natural history of severe chronic fatigue syndrome

1999 ◽  
Vol 80 (9) ◽  
pp. 1090-1094 ◽  
Author(s):  
Nancy F. Hill ◽  
Lana A. Tiersky ◽  
Vanessa R. Scavalla ◽  
Marc Lavietes ◽  
Benjamin H. Natelson
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Natural History ◽  
Chronic Fatigue ◽  
Fatigue Syndrome ◽  
History Of

scholarly journals A Multicenter Blinded Analysis Indicates No Association between Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and either Xenotropic Murine Leukemia Virus-Related Virus or Polytropic Murine Leukemia Virus

mBio ◽  
2012 ◽  
Vol 3 (5) ◽  
Author(s):  
Harvey J. Alter ◽  
Judy A. Mikovits ◽  
William M. Switzer ◽  
Francis W. Ruscetti ◽  
Shyh-Ching Lo ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Chronic Fatigue ◽  
Myalgic Encephalomyelitis ◽  
Xenotropic Murine Leukemia ◽  
Fatigue Syndrome ◽  
Related Virus ◽  
Murine Leukemia ◽  
Polytropic Murine Leukemia Virus

ABSTRACT The disabling disorder known as chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) has been linked in two independent studies to infection with xenotropic murine leukemia virus-related virus (XMRV) and polytropic murine leukemia virus (pMLV). Although the associations were not confirmed in subsequent studies by other investigators, patients continue to question the consensus of the scientific community in rejecting the validity of the association. Here we report blinded analysis of peripheral blood from a rigorously characterized, geographically diverse population of 147 patients with CFS/ME and 146 healthy subjects by the investigators describing the original association. This analysis reveals no evidence of either XMRV or pMLV infection. IMPORTANCE Chronic fatigue syndrome/myalgic encephalomyelitis has an estimated prevalence of 42/10,000 in the United States, with annual direct medical costs of $7 billion. Here, the original investigators who found XMRV and pMLV (polytropic murine leukemia virus) in blood of subjects with this disorder report that this association is not confirmed in a blinded analysis of samples from rigorously characterized subjects. The increasing frequency with which molecular methods are used for pathogen discovery poses new challenges to public health and support of science. It is imperative that strategies be developed to rapidly and coherently address discoveries so that they can be carried forward for translation to clinical medicine or abandoned to focus resource investment more productively. Our study provides a paradigm for pathogen dediscovery that may be helpful to others working in this field.

scholarly journals Xenotropic Murine Leukemia Virus–Related Virus Prevalence in Patients with Chronic Fatigue Syndrome or Chronic Immunomodulatory Conditions

2010 ◽  
Vol 202 (10) ◽  
pp. 1478-1481 ◽  
Author(s):  
Timothy J. Henrich ◽  
Jonathan Z. Li ◽  
Donna Felsenstein ◽  
Camille N. Kotton ◽  
Robert M. Plenge ◽  
...  
Keyword(s):  
Chronic Fatigue Syndrome ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Chronic Fatigue ◽  
Virus Prevalence ◽  
Xenotropic Murine Leukemia ◽  
Fatigue Syndrome ◽  
Related Virus ◽  
Murine Leukemia
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