MURINE RETROVIRUS INFECTION AND THE EFFECT OF CHRONIC ALCOHOL CONSUMPTION: PROTEOMIC ANALYSIS OF CARDIAC PROTEIN EXPRESSION
http://alcalc.oxfordjournals.org/content/38/2/103.full
some highlights:
Aims: The cardiovascular complications of acquired immunodeficiency syndrome (AIDS) are serious, including the occurrence of pathological heart conditions such as cardiomyopathy. Chronic alcohol consumption accentuates the severity of AIDS and may contribute to the development of cardiomyopathy. The aim of this work was to use a proteomics approach to investigate global alterations in protein expression in a mouse model of AIDS in the presence or absence of chronic alcohol consumption. ... Results: A number of specific proteins were observed to be differentially expressed in the mouse heart due to the effect of ethanol feeding alone. Differentially expressed proteins were also observed that were due to viral infection alone. Ethanol feeding and viral infection appeared to have similar effects on the expression of a number of proteins. A total of 24 proteins were altered by infection alone. Of these 24 proteins, eight were affected by alcohol, with six alterations being ameliorated and two being exacerbated by alcohol. Two of these proteins have been identified as the 27 kDa heat-shock protein and mitochondrial long-chain acyl-CoA thioesterase 1. Conclusions: These results suggest that chronic alcohol consumption may exacerbate the effects of viral infection on the heart by lowering the stress response leading to de-protection and further cytotoxic effects.
INTRODUCTION
in this study, we used a proteomic approach to investigate a murine model of acquired immunodeficiency syndrome (AIDS) induced by LP-BM5 leukaemia virus (MuLV). LP-BM5 MuLV-infected mice characteristically develop hypergamma-globulinaemia, splenomegaly, lymphadenopathy, T-cell functional deficiency, B-cell dysfunction, and, in the later stages, neurological signs including paralysis as well as susceptibility to opportunistic infections (Liang et al., 1996). The similarities between murine AIDS and human AIDS are striking, with similar changes in immune functions, T-cell differentiation, cytokine production, disease resistance and oxidative stress.
DISCUSSION
The murine model of AIDS induced by LP-BM5 leukaemia virus displays a number of features of human AIDS (Liang et al., 1996), and has been a useful tool for the investigation of retrovirus-induced immunodeficiency and the effects of ethanol as an accelerating cofactor (Fitzpatrick et al., 1995). This study represents the first proteomic analysis of global protein alterations in the murine model of AIDS induced by LP-BM5 leukaemia virus. Using a proteomic approach, we have demonstrated that the expression of a number of cardiac proteins is significantly altered upon viral infection
As might be expected, the comparison of the uninfected and infected, ethanol-treated mice (which indicated spots altered due to infection or ethanol or a combined effect of ethanol and infection) produced the largest number of protein expression changes 53 proteins were reduced and 15 were increased in the infected, ethanol-treated group. In a number of cases, the effect of infection mirrored that of alcohol. In most cases, the effect of the combination of alcohol and infection did not increase or decrease the effect of either treatment in isolation. Such examples are spots 536 and 482 shown in Fig. 2. It is not clear why this should be the case, but it is possible that these proteins may be part of the stress response, which may be activated in a similar fashion by both infection and alcohol feeding.
It is interesting to note that, of the 24 proteins shown to be altered in expression in the heart due to LP-BM5 infection alone, eight appeared to be further altered by ethanol feeding. However, of these eight proteins, the majority (six) were ameliorated by ethanol and for only two was the effect of infection exacerbated by ethanol. This may appear to indicate that alcohol could produce a level of cardiac protection from the virus, which would perhaps contradict the tenet that ethanol consumption aggravates the effects of AIDS. However, if these proteins represent part of a protective response to viral infection it is possible that the effect of alcohol consumption may lead to a de-protection of the cardiac myocyte and a consequent aggravation of the effects of infection. Indeed, one of the proteins altered in response to ethanol feeding was identified as the 27 kDa HSP27. It is possible, therefore, that ethanol consumption may accentuate the effects of retroviral infection in the heart by down-regulating the antiviral response and thereby compromising the ability of the cardiac myocyte to protect itself against the effect of viral damage.
http://alcalc.oxfordjournals.org/content/38/2/103.full
some highlights:
Aims: The cardiovascular complications of acquired immunodeficiency syndrome (AIDS) are serious, including the occurrence of pathological heart conditions such as cardiomyopathy. Chronic alcohol consumption accentuates the severity of AIDS and may contribute to the development of cardiomyopathy. The aim of this work was to use a proteomics approach to investigate global alterations in protein expression in a mouse model of AIDS in the presence or absence of chronic alcohol consumption. ... Results: A number of specific proteins were observed to be differentially expressed in the mouse heart due to the effect of ethanol feeding alone. Differentially expressed proteins were also observed that were due to viral infection alone. Ethanol feeding and viral infection appeared to have similar effects on the expression of a number of proteins. A total of 24 proteins were altered by infection alone. Of these 24 proteins, eight were affected by alcohol, with six alterations being ameliorated and two being exacerbated by alcohol. Two of these proteins have been identified as the 27 kDa heat-shock protein and mitochondrial long-chain acyl-CoA thioesterase 1. Conclusions: These results suggest that chronic alcohol consumption may exacerbate the effects of viral infection on the heart by lowering the stress response leading to de-protection and further cytotoxic effects.
INTRODUCTION
in this study, we used a proteomic approach to investigate a murine model of acquired immunodeficiency syndrome (AIDS) induced by LP-BM5 leukaemia virus (MuLV). LP-BM5 MuLV-infected mice characteristically develop hypergamma-globulinaemia, splenomegaly, lymphadenopathy, T-cell functional deficiency, B-cell dysfunction, and, in the later stages, neurological signs including paralysis as well as susceptibility to opportunistic infections (Liang et al., 1996). The similarities between murine AIDS and human AIDS are striking, with similar changes in immune functions, T-cell differentiation, cytokine production, disease resistance and oxidative stress.
DISCUSSION
The murine model of AIDS induced by LP-BM5 leukaemia virus displays a number of features of human AIDS (Liang et al., 1996), and has been a useful tool for the investigation of retrovirus-induced immunodeficiency and the effects of ethanol as an accelerating cofactor (Fitzpatrick et al., 1995). This study represents the first proteomic analysis of global protein alterations in the murine model of AIDS induced by LP-BM5 leukaemia virus. Using a proteomic approach, we have demonstrated that the expression of a number of cardiac proteins is significantly altered upon viral infection
As might be expected, the comparison of the uninfected and infected, ethanol-treated mice (which indicated spots altered due to infection or ethanol or a combined effect of ethanol and infection) produced the largest number of protein expression changes 53 proteins were reduced and 15 were increased in the infected, ethanol-treated group. In a number of cases, the effect of infection mirrored that of alcohol. In most cases, the effect of the combination of alcohol and infection did not increase or decrease the effect of either treatment in isolation. Such examples are spots 536 and 482 shown in Fig. 2. It is not clear why this should be the case, but it is possible that these proteins may be part of the stress response, which may be activated in a similar fashion by both infection and alcohol feeding.
It is interesting to note that, of the 24 proteins shown to be altered in expression in the heart due to LP-BM5 infection alone, eight appeared to be further altered by ethanol feeding. However, of these eight proteins, the majority (six) were ameliorated by ethanol and for only two was the effect of infection exacerbated by ethanol. This may appear to indicate that alcohol could produce a level of cardiac protection from the virus, which would perhaps contradict the tenet that ethanol consumption aggravates the effects of AIDS. However, if these proteins represent part of a protective response to viral infection it is possible that the effect of alcohol consumption may lead to a de-protection of the cardiac myocyte and a consequent aggravation of the effects of infection. Indeed, one of the proteins altered in response to ethanol feeding was identified as the 27 kDa HSP27. It is possible, therefore, that ethanol consumption may accentuate the effects of retroviral infection in the heart by down-regulating the antiviral response and thereby compromising the ability of the cardiac myocyte to protect itself against the effect of viral damage.
