Een studie waarin XMRV-geinfekteerde resusaapjes lange tijd bestudeerd werden,
toont aan dat:
- XMRV al vrij snel "niet" meer in het bloed terug te vinden is (PCR, antilichamen), maar
lange tijd daarna nog wel aanwezig is in het bloed (zonder sterke antilichaam-reaktie)
- het virus zich al vrij snel diverse soorten weefsels nestelt (bijv. darmslijmvlies),
met een voorkeur voor specifieke cellen in verschillende typen weefsels, en
- de infektie mogelijk (zeer) lange tijd niet tot symptomen ("ziekte") leidt,
hetgeen samen met de
invloed van inspanning/stress op XMRV-infecties,
zou kunnen verklaren waarom iemand pas jaren later ziek wordt én ziek blijft.
XMRV: Study Shows Virus Can Cause 'Persistent Infection' in Monkeys.
By Amy Dockser Marcus
"The virus causes chronic, persistent infection," says Robert Silverman ...
Moreover, the new research suggests that in these monkeys, at least,
the virus can be difficult to detect in blood, even though it’s taken root in the body.
The animals showed signs of the virus in their blood right after being infected,
but very soon afterward, those signs disappeared, making detection very tough.
When monkeys were autopsied, however, organs including the spleen, lungs, and prostate contained XMRV-infected cells.
XMRV infection of Rhesus macaques
17 February 2011
By Vincent Racaniello
The subject of this study, the Rhesus macaque (Macaca mulatta),
was selected because of its evolutionary proximity to humans and a comparable immune system.
Of three animals infected,
virus was detected in one animal at day 4 and not after day 14;
and in a second animal from days 14-20.
The third animal did not develop detectable viremia.
Proviral DNA was found in peripheral blood mononuclear cells (PBMC) of all three monkeys for 3-4 weeks, indicating successful infection.
At one month post-infection proviral DNA was no longer detected.
Plasma virus was again detected in one of the positive animals on day 291,
16 days after being immunized with a mixture of XMRV proteins.
This means that viral DNA had been present in this animal but was not detected.
XMRV was detected in CD4+ and CD8+ T cells and NK cells, but not in B cells or monocytes.
Rhesus macaques infected with XMRV did not display obvious clinical symptoms.
Analysis of peripheral blood revealed increases in the number of circulating B and NK cells.
Antiviral antibody titers were detected after infection and re-infection of animals but soon decreased.
Other infected animals were sacrificed during the acute phase of infection
to identify pathological changes and sites of virus replication.
No pathogenic consequences were observed except for the formation of germinal centers in spleen and lymphoid organs,
changes that are expected after immune stimulation.
Virus was detected in a wide variety of tissues,
including spleen, lymph nodes, the lining of the gastrointestinal tract, prostate, testis, cervix, vagina, and pancreas,
but not in others including brain, heart, kidney, and bladder.
Different types of cells were infected in different tissues:
lymphocytes in lymphoid organs, macrophages in lung, epithelial or interstitial cells in other organs.
The authors note that "this viral behavior appears specific to this virus".
Infection, viral dissemination and antibody responses of rhesus macaques exposed to the human gammaretrovirus XMRV.
J. Virol. doi:10.1128/JVI.02411-10.
Nattawat Onlamoon, Jaydip Das Gupta, Prachi Sharma, Kenneth Rogers, Suganthi Suppiah, Jeanne Rhea, Ross J. Molinaro, Christina Gaughan, Beihua Dong, Eric A. Klein, Xiaoxing Qiu, Sushil Devare, Gerald Schochetman, John Hackett Jr., Robert H Silverman, and François Villinger
was identified in association with human prostate cancer and chronic fatigue syndrome.
the infection potential, kinetics, and tissue distribution of XMRV in an animal model,
we inoculated 5 macaques with XMRV intravenously.
a persistent chronic disseminated infection,
with low transient viremia and provirus in blood lymphocytes during acute infection.
Although undetectable in blood after about a month,
XMRV viremia was reactivated at 9 month
confirming the chronicity of the infection.
XMRV gag was detected in tissues throughout,
with wide dissemination throughout the entire period of monitoring.
XMRV infection showed organ specific cell tropism:
CD4 T cells in lymphoid organs
including the gastrointestinal lamina propria, alveolar macrophages in lung, and
epithelial/interstitial cells in other organs, including the reproductive tract.
in spite of the intravenous inoculation,
extensive XMRV replication was noted in prostate
during acute but not chronic infection,
even though infected cells were still detectable
by FISH in prostate at 5 and 9 months post infection.
Marked lymphocyte activation occurred immediately post infection,
but antigen specific cellular responses were undetectable.
Antibody responses were elicited and boosted upon reexposure,
but titers decreased rapidly
suggesting low antigen stimulation over time.
Our findings establish a nonhuman primate model to study
XMRV replication/dissemination, transmission, pathogenesis, immune responses and
potential future therapies.