XMRV might be transmitted via Coughing

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Thanks to Dr Speedy

who runs the *THE NICEGUIDELINES BLOG*

*Doctor Speedy and ME in search of medical

honesty*

at: http://niceguidelines.blogspot.com

He draw my attention to the study below:

The full pdf article can be found at:

http://www.cdc.gov/eid/content/16/6/pdfs/10-0066.pdf

But is attached for private members

List members can find the Table & Figure at the

address above - but when they only will see the

table & figure, they can find them at:

http://rapidshare.com/files/389008829/Table-Detection_of_XMRV_in_respiratory_tra\

ct.jpg

and:

http://rapidshare.com/files/389008830/Figure._Xenotropic_murine_leukemia_virus.j\

pg

~jvR

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Tuesday, May 18, 2010

*XMRV might be transmitted via coughing*

Dr Fischer, Institute for Medical Microbiology and

Virology at the University Medical Center

Hamburg-Eppendorf, Germany

German study finds that XMRV or

virus-infected cells might be carried in

and transmitted by the respiratory tract.

````

http://www.cdc.gov/eid/content/16/6/pdfs/10-0066.pdf

DOI: 10.3201/eid1606.100066

Suggested citation for this article: Fischer N, Schulz

C, Stieler K, Hohn O, Lange C, Drosten C, et al.

Xenotropic murine leukemia virus–related

gammaretrovirus in respiratory tract. Emerg Infect

Dis. 2010 Jun; [Epub ahead of print]

Xenotropic Murine Leukemia

Virus–related Gammaretrovirus

in Respiratory Tract

Fischer, Schulz,

Stieler, Oliver Hohn, Christoph Lange,

Christian Drosten, and Aepfelbacher

Author affiliations:

University Medical Center Hamburg-Eppendorf,

Hamburg, Germany (N. Fischer, C. Schulz, K. Stieler,

M. Aepfelbacher); Koch-Institute, Berlin,

Germany (O. Hohn); Leibniz-Center for Medicine and

Biosciences, Borstel, Germany (C. Lange); and

University of Bonn Medical Centre, Bonn, Germany

(C. Drosten)

Xenotropic murine leukemia virus–related

gammaretrovirus (XMRV) has been recently

associated with prostate cancer and chronic fatigue

syndrome. To identify nucleic acid sequences, we

examined respiratory secretions by using PCR.

XMRV-specific sequences were detected in 2%–3% of

samples from 168 immunocompetent carriers and

~10% of samples from 161 immunocompromised

patients.

Xenotropic murine leukemia virus–related

gammaretrovirus (XMRV) was originally discovered in

tissue from patients with familial prostate cancer

homozygous for a missense mutation in the RNase L

gene, R462Q (1).

Detection of viral nucleic acid in tissue sections of

cancerous prostate glands and cloning of the viral

integration sites confirmed XMRV as a bona fide

human infection with a murine leukemia

virus–related retrovirus (1).

Whether XMRV is actively involved in prostate cancer

tumorigenesis or whether it is just a bystander virus

(2,3) remains unclear.

On the basis of its close homology (up to 94% nt

identity) to endogenous and exogenous full-length

sequences from Mus musculus mice (1), XMRV most

likely originated in mice, although they are probably

not the current reservoir of infection (4).

Recent findings of XMRV sequences in up to 67% of

peripheral blood mononuclear cells (PBMCs) of

patients with chronic fatigue syndrome and in 3.4%

of PBMCs of healthy controls raise the question

whether XMRV could be a blood-borne pathogen (5).

However, the finding of XMRV in PBMCs from patients

with chronic fatigue syndrome is controversial

because multiple studies in Europe have failed to

detect XMRV (6–8).

Similarly, frequency of XMRV in prostate cancer

samples ranges from 0 to 23%, depending on

geographic restriction of the virus or, more likely,

diagnostic techniques used (PCR, quantitative PCR,

immunohistochemistry) (1–3,9,10).

Indirect evidence has suggested sexual transmission

(9). Questions remain about worldwide distribution,

host range, transmission routes, and organ tropism

of the virus.

To begin to answer some of them, we looked for

XMRV in respiratory samples from 267 patients with

respiratory tract infection (RTI) and 62 healthy

persons.

The Study

During 2006–2009, the 267 samples were collected

from 3 groups of patients (Table). Group 1 comprised

patients who had traveled from Asia to Germany;

location of their permanent residency was unknown.

Groups 2 and 3 and the control group comprised only

persons from northern Germany. From group 1, a

total of 75 sputum and nasal swab specimens were

collected from patients who had unconnected cases

of RTI and who had recently traveled by air (11).

From group 2, a total of 31 bronchoalveolar lavage

(BAL) samples were collected from patients with

chronic obstructive pulmonary disease (defined by a

forced expiratory volume in 1 second/forced vital

capacity <70% and forced expiratory volume in 1

second <80% of the predicted value) who had signs

of RTI.

From group 3, a total of 161 BAL and tracheal

secretion samples were collected from patients with

severe RTI and immunosuppression as a result of

solid organ or bone marrow transplantation.

From the control group, throat swabs were collected

from 52 healthy persons and BAL samples were

collected from 10 healthy volunteers who had no

signs of RTI and no known underlying disease.

All samples were analyzed by culture for pathogenic

bacteria and fungi and by PCR for rhinoviruses,

adenoviruses, enteroviruses, influenza viruses A and

B, parainfluenza viruses 1–3, respiratory syncytial

virus, cytomegalovirus, Epstein-Barr virus, and

human metapneumovirus.

All samples were tested in duplicates obtained by

individual RNA extractions. XMRV RNA was reverse

transcribed from total RNA, after which nested PCR

or real-time PCR were conducted as recently

described (1,12).

No serum samples were available from these

patients to confirm the results by serologic testing.

For group 1, XMRV-specific sequences were detected

with relatively low frequency (2.3%).

For group 2, XMRV-specific sequences were amplified

in 1 BAL sample, which was also positive for

Staphylococcus aureus by routine culture methods.

For group 3, XMRV-specific sequences were detected

at a frequency of 9.9%, which was significantly

higher than that for the healthy control group (3.2%)

at the 90% confidence level but not at the 95% level

(p = 0.078, 1 sample t-test).

Of 16 group 3 samples, 10 showed no signs of

co-infection. The remaining 6 samples showed

co-infection with rhinovirus or adenovirus (1 sample

each); S. aureus (3 samples); or mixed infection with

pathogenic fungi, Candida albicans and Asperigillus

fumigatus (1 sample).

All samples that were positive for XMRV by

gag-nested PCR, together with a set of those that

were negative for XMRV, were retested by real-time

PCR. Results showed low XMRV RNA concentrations,

103 –104/mL of specimen.

To confirm the validity of XMRV detection, a subset

of 6 specimens (3 XMRV positive and 3 XMRV

negative) were tested by using an alternative PCR

assay for viral RNA (3) and a C-Type RT Activity Kit

(Cavidi, Uppsala, Sweden) for type C reverse-

transcription activity.

XMRV sequences from alternative targets in the gag

and env regions were confirmed in 2 of the 3

XMRV-positive samples but in none of the controls.

One XMRV-positive BAL specimen showed an 8-fold

increase above background of specific type C

retroviral reverse-transcriptase activity, suggesting

presence of active type C retrovirus within this

sample. This assay is substantially less sensitive

than reverse transcription–PCR.

All XMRV gag sequences (390-bp fragment) were

98%–99% identical to previously published XMRV

sequences from persons with prostate cancer (1,2).

Phylogenetic analysis showed close clustering

(Figure).

Conclusions

XMRV, originally identified in RNase L–deficient

patients with familial prostate cancer, has gained

interest since recent work showed its protein

expression in as many as 23% of prostate cancer

cases (10) and XMRV-specific sequences were

detected in PBMCs of 67% patients with chronic

fatigue syndrome (5).

These results, however, could not be confirmed by

others (6–8). Both studies also detected XMRV

protein or sequences in their control cohorts with

frequencies of 6% and 4%, respectively.

Among the most pressing information gaps with

regard to XMRV is its preferred route of transmission.

Detection of XMRV in PBMCs and plasma of patients

with chronic fatigue syndrome raises the possibility

of blood-borne transmission; sexual transmission has

also been hypothesized on the basis of indirect

evidence (5,9).

We detected XMRV in respiratory secretions of

immunocompetent patients with and without RTI at

a frequency of ~3.2%, which is in good concordance

with the recently reported prevalence in the general

population of up to 4% (5).

Frequency of XMRV detection in group 1 patients

(2.25%) was comparable to that of human

metapneumovirus and rhinovirus within this group

and considerably less frequent than that of

parainfluenzavirus (15.5%) or influenza A virus

(7.6%) detection (11).

Our findings indicate that XMRV or virus-infected

cells might be carried in and transmitted by the

respiratory tract.

Attempts to isolate infectious virus from XMRV

sequence–positive respiratory samples failed,

possibly because of inadequate storage of samples

before virus culturing attempts or relatively low copy

numbers of the virus within the samples.

Thus, whether the respiratory tract serves as a

putative transmission route for XMRV cannot be

determined at this time.

The observed increase in prevalence among

immunosuppressed patients with RTI suggests that

XMRV might be reactivated in absence of an efficient

antiviral defense.

Together with earlier observations on increased

XMRV replication in RNase L–deficient cells (1,12),

this finding implies that the immune system plays a

role in controlling XMRV replication.

It remains unknown whether immunosuppression

predisposes a patient to secrete infectious XMRV

from the respiratory tract or whether presence of

virus might be meaningless for epidemiology in a

way similar to HIV-1 (15).

Future studies should address whether the

respiratory tract might serve as a source of XMRV

infection or whether immunosuppression might cause

an increased risk for primary infection.

This study was supported by the Werner Otto

Stiftung grant no. 4/69 to N.F. The study was

approved by the ethics committee at the board of

physicians of the Free and Hanseatic City of

Hamburg (No.WF-005/09).

Dr Fischer works as a group leader at the Institute

for Medical Microbiology and Virology at the

University Medical Center Hamburg-Eppendorf.

Her main research interests are emerging viruses,

in particular the gammaretrovirus XMRV.

References

1. Urisman A, Molinaro RJ, Fischer N, Plummer SJ,

Casey G, Klein EA, et al. Identification of a novel

gammaretrovirus in prostate tumors of patients

homozygous for R462Q RNASEL variant. PLoS Pathog.

2006;2:e25. PubMed DOI:

10.1371/journal.ppat.0020025 - http://bit.ly/9k8txI

2. Fischer N, Hellwinkel O, Schulz C, Chun FK, Huland

H, Aepfelbacher M, et al. Prevalence of human

gammaretrovirus XMRV in sporadic prostate cancer. J

Clin Virol. 2008;43:277–83. PubMed DOI:

10.1016/j.jcv.2008.04.016 - http://bit.ly/a9kYiL

3. Hohn O, Krause H, Barbarotto P, Niederstadt L,

Beimforde N, Denner J, et al. Lack of evidence for

xenotropic murine leukemia virus–related virus

(XMRV) in German prostate cancer patients.

Retrovirology. 2009;6:92. PubMed DOI:

10.1186/1742-4690-6-65 - http://bit.ly/bLi3mC

4. Stieler KSC, Lavanya M, Aepfelbacher M, Stocking

C, Fischer N. Host range and cellular tropism of the

human exogenous gammaretrovirus XMRV. Virology.

2010:399:23–30.

5. Lombardi VC, Ruscetti FW, Das Gupta J, Pfost MA,

Hagen KS, DL, et al. Detection of an

infectious retrovirus, XMRV, in blood cells of patients

with chronic fatigue syndrome. Science.

2009;326:530–1.

6. Erlwein O, Kaye S, McClure MO, Weber J, Wills G,

Collier D, et al. Failure to detect the novel retrovirus

XMRV in chronic fatigue syndrome. PLoS One.

2010;5:e8519.

7. Groom HC, Boucherit VC, Makinson K, Randal E,

Baptista S, Hagan S, et al. Absence of xenotropic

murine leukaemia virus–related virus in UK patients

with chronic fatigue syndrome. Retrovirology.

2010;7:10.

8. van Kuppeveld FJ, de Jong AS, Lanke KH,

Verhaegh GW, Melchers WJ, Swanink CM, et al.

Prevalence of xenotropic murine leukaemia

virus–related virus in patients with chronic fatigue

syndrome in the Netherlands: retrospective analysis

of samples from an established cohort. BMJ.

2010;340:c1018.

9. Hong S, Klein EA, Das Gupta J, Hanke K, Weight

CJ, Nguyen C,et al. Fibrils of prostatic acid

phosphatase fragments boost infections with XMRV

(xenotropic murine leukemia virus–related virus), a

human retrovirus associated with prostate cancer. J

Virol. 2009;83:6995–7003. PubMed DOI:

10.1128/JVI.00268-09 - http://bit.ly/9j0tnf

Address for correspondence:

Fischer, Institute for Medical Microbiology and

Virology, University Medical Center Hamburg-

Eppendorf, istrasse 52, 20246 Hamburg,

Germany; email: nfischer@...

Table-Detection of XMRV in respiratory tract

Figure. Xenotropic murine leukemia virus–related

gammaretrovirus (XMRV) gag sequences derived from

respiratory tract secretions. Phylogenetic tree

comparing the 390-nt gag fragment of all respiratory

samples of this study with recently published XMRV

sequences from patients with familial prostate

cancer (1). The edited sequences were aligned with

ClustalX version 1.82 (13,14) by using default

settings. The tree was generated on the basis of

positions without gaps only. Sequences are labeled

as X, xenotropic; P, polytropic; mP, modified

polytropic; S, sputum, IS, immunosuppression; TS,

tracheal secretion; and C, control. Scale bar indicates

nucleotide substitutions per position