ook andere HIV-medicijnen

lijken werkzaam tegen XMRV






Volgens een recente studie van Smith et al. zijn, naast AZT (klik hier), tenofovir (klik hier),

de reverse transcriptase-remmers 3'-azido-2',3'-dideoxyadenosine, 3'-azido-2',3'-dideoxyguanosi-ne en adefovir, en de integrase-remmers raltegravir and elvitegravir ook werkzaam tegen XMRV,

althans in vitro (buiten het lichaam, bijv. in een reageerbuis).


XMRV lijkt resistent tegen

(specifieke) non-nucleoside reverse transcriptase-remmers (nevirapine and efavirenz) en

(specifieke) proteaseremmers.





In essentie kan het retrovirus momenteel op vier momenten gestopt worden (zie afbeelding):

  • bij het aanhaken bij de cel (bindings- en toegangsremmers),
  • bij het produceren van DNA uit RNA (reverse transcriptase-remmers),door
    • m.b.v. nucleoside analoge reverse transcriptase-remmers;
    • m.b.v. nucleotide analoge reverse transcriptase-remmers; en
    • m.b.v. non-nucleoside reverse transcriptase-remmers;
  • bij het integreren van het virale DNA in het DNA van de gastheer (integraseremmers) en
  • bij het knippen van RNA: het ontstaan van een nieuw virus (proteaseremmers).


Het lijkt er vooralsnog op dat bepaalde soorten reverse transcriptase-remmers (type I en type II) en (specifieke) integraseremmers werken. (Specifieke) protease-remmers werken kennelijk niet.

Onderzoek naar de werking van bindings- en toegangsremmers m.b.t. XMRV is mij niet bekend.




Citaten uit de studie:



A growing body of evidence suggests that XMRV

is intrinsically resistant to many of the drugs used to treat HIV-1 infection,

but is sensitive to a small subset of antiretroviral inhibitors.


[Eerdere studies waaraan gerefereerd wordt, zijn onder meer: 


Our analysis demonstrates that XMRV is sensitive to a broader range of NRTIs than was previously appreciated; these include analogs that are used in the clinical treatment of HIV-1 infection (AZT and tenofovir) as well as other structurally-related NRTIs (AZddA, AZddG and adefovir).


We observed a distinct pattern of NRTI sensitivity in XMRV that correlates with the structure of the pseudosugar moiety; while XMRV is sensitive to 3'-azido nucleoside analogs and acyclic nucleoside phosphonates, the virus is moderately resistant to dideoxynucleosides and highly resistant to L-form thiacytidine NRTIs. Importantly, this pattern suggests that other 3'-azido or acyclic nucleoside analogs might also exhibit anti-XMRV activity.


In addition, our data show that elvitegravir blocks XMRV infection with a degree of potency similar to that of AZT.


This finding expands the number of integrase inhibitors with known activity against XMRV in vitro [buiten het lichaam, bijv. in een reageerbuis].


While our use of the same target cell type for XMRV and HIV-1 provides an important reference point for characterizing XMRV drug susceptibility, we note that the two viruses utilize different receptors for entry and are therefore likely to infect differing host cell types in vivo [in het lichaam].


Ultimately, the clinical utility of antiretrovirals for XMRV will depend on drug distribution and metabolism at anatomic sites of XMRV replication, the degree to which antiretrovirals reduce XMRV viral load, and whether reductions in viral load slow pathogenesis.


In the event that XMRV is shown to be the causative agent of human disease, our data identify candidate drugs for clinical studies of antiretroviral therapy in XMRV-infected patients.




Susceptibility of the human retrovirus XMRV to antiretroviral inhibitors.

Retrovirology 2010, 7:70. doi:10.1186/1742-4690-7-70.

Robert A Smith, Geoffrey S Gottlieb, A Dusty Miller


Published: 31 August 2010


Abstract (provisional)





XMRV (xenotropic murine leukemia virus-related virus)

is the first known example of

an exogenous gammaretrovirus

that can infect humans.


A limited number of reports

suggest that

XMRV is intrinsically resistant to

many of the antiretroviral drugs used to treat HIV-1 infection,

but is sensitive to a small subset of these inhibitors.


In the present study,

we used a novel marker transfer assay

to directly compare

the antiviral drug sensitivities of

XMRV and HIV-1

under identical conditions

in the same host cell type.





We extend the findings of previous studies by showing that,

in addition to AZT and tenofovir,

XMRV and HIV-1

are equally sensitive to

AZddA (3'-azido-2',3'-dideoxyadenosine),

AZddG (3'-azido-2',3'-dideoxyguanosine) and



These results indicate that

specific 3'-azido or acyclic nucleoside analog

inhibitors of

HIV-1 reverse transcriptase (RT)

also block XMRV infection

with comparable efficacy in vitro.


Our data confirm that


is highly resistant to

the non-nucleoside RT inhibitors

nevirapine and efavirenz and

to inhibitors of

HIV-1 protease.


In addition,

we show that

the integrase inhibitors

raltegravir and elvitegravir

are active against XMRV,

with EC50 values in the nanomolar range.





Our analysis demonstrates


XMRV exhibits

a distinct pattern of

nucleoside analog susceptibility

that correlates with

the structure of

the pseudosugar moiety and



is sensitive to

a broader range of

antiretroviral drugs

than has previously been reported.


We suggest that

the divergent drug sensitivity profiles of

XMRV and HIV-1

are partially explained by

specific amino acid differences

in their respective protease,

RT and

integrase sequences.


Our data provide

a basis for

choosing specific antiretroviral drugs

for clinical studies

in XMRV-infected patients.



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