Contributions
Abstract: P1000
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 16 Microbiology and Virology
Introduction: The aetiology of Multiple Sclerosis (MS) is still unknown, but there is strong evidence that environmental factors can trigger the disease on the background of genetic predisposition. Human Endogenous Retroviruses (HERVs) are strongly associated with MS: in normal conditions HERVs are silenced or expressed at low levels, but in some pathological conditions, like MS, their expression is higher than in the healthy population. A link between HERVs and MS may also be supported by the observation that people infected by the human retrovirus HIV may have a lower risk of developing MS than the non-infected, healthy population. We hypothesised that Antiretroviral therapies (ART) could inhibit the expression of HERVs in addition to HIV, thus educing the probability to develop MS. In a pilot study, a small cohort of HIV+ patients that were either treated or not with ART was recruited to study the effect of antiretroviral drugs on the expression of human MS-related retrovirus (MSRV)/HERV-W ex vivo. In parallel, the same classes of drug were used to test their efficacy in MSRV/HERV-W inhibition in vitro.
Methods: MSRV/HERV-Wenv and Toll-like receptor 4 (TLR4) RNA expression were analysed by Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 9 HIV-infected patients and compared with 23 Healthy Controls (HC) and 23 MS patients. RNA and protein expression of MSRV/HERV-Wenv were also measured by RT-PCR and by Flow Cytometry in lymphoblastoid cell lines (LCL) treated with 10µM, 1µM, 0,1µM of different classes of ART (Lamivudine, Tenofovir, Daranuvir, Efavirenz and Raltegravir) in vitro.
Results: We found that the expression of MSRV/HERV-Wenv RNA in HIV-infected people was lower than in MS patients and similar to HC, while the expression of TLR4 was higher in HIV-infected people than in HC and MS. However, there was no difference in MSRV/HERV-Wenv expression between antiretroviral drug -treated and -untreated HIV patients. The expression of MSRV/HERV-Wenv in treated LCL was reduced only by Efavirenz (non-nucleoside reverse transcriptase inhibitors) and by the combined ART.
Conclusions: Some ART may prevent HERV expression. Further experiments are needed to clarify the potential role of ART in conferring protection from MS.
Disclosure:
Elena Morandi: nothing to disclose
Tim Constantin-Teodosiu: nothing to disclose
Rachael Tarlinton: nothing to disclose
Bruno Gran: has received unrestricted grants to conduct MS-related research and to attend scientific conferences from Merck Serono, Teva UK, Biogen, Novartis, Bayer Schering and Genzyme. He has been an advisor to Merck Serono, Teva UK, and Roche.
Abstract: P1000
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 16 Microbiology and Virology
Introduction: The aetiology of Multiple Sclerosis (MS) is still unknown, but there is strong evidence that environmental factors can trigger the disease on the background of genetic predisposition. Human Endogenous Retroviruses (HERVs) are strongly associated with MS: in normal conditions HERVs are silenced or expressed at low levels, but in some pathological conditions, like MS, their expression is higher than in the healthy population. A link between HERVs and MS may also be supported by the observation that people infected by the human retrovirus HIV may have a lower risk of developing MS than the non-infected, healthy population. We hypothesised that Antiretroviral therapies (ART) could inhibit the expression of HERVs in addition to HIV, thus educing the probability to develop MS. In a pilot study, a small cohort of HIV+ patients that were either treated or not with ART was recruited to study the effect of antiretroviral drugs on the expression of human MS-related retrovirus (MSRV)/HERV-W ex vivo. In parallel, the same classes of drug were used to test their efficacy in MSRV/HERV-W inhibition in vitro.
Methods: MSRV/HERV-Wenv and Toll-like receptor 4 (TLR4) RNA expression were analysed by Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 9 HIV-infected patients and compared with 23 Healthy Controls (HC) and 23 MS patients. RNA and protein expression of MSRV/HERV-Wenv were also measured by RT-PCR and by Flow Cytometry in lymphoblastoid cell lines (LCL) treated with 10µM, 1µM, 0,1µM of different classes of ART (Lamivudine, Tenofovir, Daranuvir, Efavirenz and Raltegravir) in vitro.
Results: We found that the expression of MSRV/HERV-Wenv RNA in HIV-infected people was lower than in MS patients and similar to HC, while the expression of TLR4 was higher in HIV-infected people than in HC and MS. However, there was no difference in MSRV/HERV-Wenv expression between antiretroviral drug -treated and -untreated HIV patients. The expression of MSRV/HERV-Wenv in treated LCL was reduced only by Efavirenz (non-nucleoside reverse transcriptase inhibitors) and by the combined ART.
Conclusions: Some ART may prevent HERV expression. Further experiments are needed to clarify the potential role of ART in conferring protection from MS.
Disclosure:
Elena Morandi: nothing to disclose
Tim Constantin-Teodosiu: nothing to disclose
Rachael Tarlinton: nothing to disclose
Bruno Gran: has received unrestricted grants to conduct MS-related research and to attend scientific conferences from Merck Serono, Teva UK, Biogen, Novartis, Bayer Schering and Genzyme. He has been an advisor to Merck Serono, Teva UK, and Roche.