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Bovine Leukemia Virus Infection is Found in at Least 1 in 3 People: Could This Immunosuppressive Retrovirus Play a Role in ME/CFS?
Bovine leukemia virus (BLV) is an immunosuppressive and cancer-causing virus from the retrovirus family, whose natural host is cows and bulls. In the US it is estimated that 44% of dairy cows and 10% of beef cattle are infected with BLV.
Until recently, BLV was not thought to infect humans, but in the last few years it has emerged that at least around 1 in 3 humans are infected with BLV.
One 2003 study found that 74% of humans have antibodies to bovine leukemia virus, so BLV's prevalence in humans could be as high as that; but the authors point out that these antibodies do not necessarily prove that humans are actually infected with the virus, because the antibodies could just be a response to heat-denatured BLV antigens consumed in food.
However, irrefutable evidence that BLV infects humans comes from a US 2015 study and an Australian 2017 study which respectively found that 29% and 41% of healthy women have bovine leukemia virus DNA in their breast tissue. So this is clear evidence that around one third of the human population at least is infected with the BLV retrovirus.
These US and Australian studies respectively found that 59% and 81% of women with breast cancer had BLV in their breast tissues, thus suggesting bovine leukemia virus may play a role in breast cancer. Although a study which sequenced the genome of some breast cancers found no evidence of BLV DNA in these tumors, which argues against the link between BLV and human breast cancer. And a study found that those who drank raw milk (were BLV is found) did not have a higher rate of cancer (but remember that BLV is already present in many humans, so then drinking raw milk provides no extra risk). At present the jury is still out regarding whether BLV can cause breast cancer.
A Possible Role for Bovine Leukemia Virus in ME/CFS?
What we are going to consider here is whether bovine leukemia virus infection in humans may have immunosuppressive effects that play a role ME/CFS. In particular, we can ask the question whether a possible immune suppression from a human BLV infection might explain why many ME/CFS patients have chronic active enterovirus or herpesvirus infections that they cannot seem to clear or keep under control?
Many doctors and researchers believe these chronically active enterovirus and herpesvirus of ME/CFS may be the cause of the disease. Could the immunosuppressive bovine leukemia virus be the hidden enabling factor behind these chronic enterovirus or herpesvirus infections? Could BLV be the reason ME/CFS patients cannot clear enterovirus or herpesvirus from their tissues, and thus cannot recover from ME/CFS? This is what we consider in the next section.
The Immunosuppressive Effects of Bovine Leukemia Virus
Bovine leukemia virus (which is also called bovine leukosis virus) is known to cause various forms of immune suppression in cows, which are as follows.
One study found that in cows, BLV induces TGF‐beta secretion from regulatory T cells (TGF‐beta in turn was found to suppress the secretion of the antiviral Th1 cytokines interferon gamma and TNF-alpha by CD4 T cells, as well as suppress natural killer cell cytotoxicity). This may allow opportunistic infections to arise.
Interestingly, we know that TGF‐beta is high in ME/CFS (this is one of the most consistent cytokine findings in ME/CFS). So that is in keeping with what BLV infection does in cows.
Another study found that in cows, BLV infection decreased secretory IgM and decreased T-cells in the blood (mainly CD4 T-cells). And a correlation was found between BLV infection and lack of spontaneous recovery from Trichophyton verrucosum (ringworm fungus) infection, indicating an immunosuppressive effect of BLV in cows. The study also notes that other BLV studies have found significant association between herd BLV infection status and disease incidence in the herd.
This study also details the B-cell and T-cell abnormalities found in cows positive for BLV. The study notes that BLV infection also negatively affects the functioning of monocytes and macrophages.
This article states that in cows, the primary cellular target of BLV infection is B-cells. Once infected with the virus, B-cell populations increase due to abnormal growth, resulting in a persistent lymphocytosis and eventually lymphomas (cancer of the lymphatic system) in cows.
BLV is closely related to the human retrovirus virus HTLV-1, and certainly in the case of human HTLV-1 infection, case studies of opportunistic infections with cytomegalovirus and herpes zoster have been reported.
So could the above immunological abnormalities found in cows explain the fact that the immune system of human ME/CFS patients seems to have trouble keeping enteroviruses and herpesviruses under control?
Well, we don't know if BLV causes in humans the same immunosuppressive effects in creates in cattle, and even if it did, the mechanism by which these effects might lead to chronic enteroviruses and herpesviruses infections is not clear. But it seems within the realm of possibility that BLV may be playing an immunosuppressive role in ME/CFS.
But it's just guessing at this stage, as very little is known about what bovine leukemia virus does in humans, because we only recently discovered this cow virus could infect humans.
How is Bovine Leukemia Virus Transmitted to Humans?
How do humans get infected with BLV? The Australian study says:
Bovine leukemia virus is present in raw unpasteurized milk, so it is possible this virus passed into human populations millennia ago, in an era long before pasteurization of milk was introduced, and is now transmitted from human to human. The human practice of drinking another animals' milk, which became common after the agricultural revolution 10,000 year ago, could have first introduced this cow virus into human populations.
And/or it is possible that humans are even today catching BLV directly from cows by consuming unpasteurized dairy or undercooked beef. At this stage we don't know how the virus gets into humans. (A study on people who consume raw milk found no increased incidence of breast cancer, though.)
Antivirals for Bovine Leukemia Virus?
Bovine leukemia virus falls within the deltaretrovirus genus. This contrasts to murine leukemia virus (MLV), feline leukemia virus (FLV) and XMRV which are from the gammaretrovirus genus.
Bovine leukemia virus is closely related to the human retrovirus virus called human T-lymphotropic virus 1 (HTLV-1), which is also found in the same deltaretrovirus genus.
Raltegravir has been shown to inhibit FLV, and also shown to inhibit MLV. Tenofovir has been shown to inhibit FLV. Elvitegravir has been shown to inhibit gammaretroviruses.
However, whether any of these antiretroviral drugs would work for BLV, I don't know. In a study on Raltegravir for HTLV-1 (the closest virus to BLV), there was little effect, with the authors noting that "lack of continuous viral replication cycles in chronic HTLV-1 carriers most likely explains our findings."
Some new research has shown that an anti-PD-1 antibody drug can reactivate the suppressed immune cells caused by BLV infection, and as the immune response is revitalized in this way, it leads to a decrease in BLV viral loads in cows.
Any Evidence for Bovine Leukemia Virus in ME/CFS?
Professor Ian Lipkin's high throughput sequencing study found retroviruses in 85% of ME/CFS patients' blood plasma samples, so this I think would be consistent with bovine leukemia virus playing a role in ME/CFS.
Dr Judy Mikovits detected gammaretrovirus proteins in ME/CFS, as well as anti-gammaretrovirus Env antibodies. I think we can confident that her XMRV findings were incorrect and due to contamination, but whether these gammaretrovirus findings still hold is another question. However, I am not sure if this offers evidence for BLV in ME/CFS, as BLV is a deltaretrovirus, not a gammaretrovirus.
Dr Elaine Defreitas found a HTLV-II-like retrovirus in ME/CFS patients, but most people could not replicate her findings, including Defreitas herself. But interestingly, HTLV-I and HTLV-II are very similar to BLV, so this makes you wonder whether the virus similar to HTLV-II that Defreitas found in ME/CFS patients might have been BLV.
An article on Defreitas's discovery of this HTLV-II-like can be found here: part 1 and part 2.
Bovine leukemia virus (BLV) is an immunosuppressive and cancer-causing virus from the retrovirus family, whose natural host is cows and bulls. In the US it is estimated that 44% of dairy cows and 10% of beef cattle are infected with BLV.
Until recently, BLV was not thought to infect humans, but in the last few years it has emerged that at least around 1 in 3 humans are infected with BLV.
One 2003 study found that 74% of humans have antibodies to bovine leukemia virus, so BLV's prevalence in humans could be as high as that; but the authors point out that these antibodies do not necessarily prove that humans are actually infected with the virus, because the antibodies could just be a response to heat-denatured BLV antigens consumed in food.
However, irrefutable evidence that BLV infects humans comes from a US 2015 study and an Australian 2017 study which respectively found that 29% and 41% of healthy women have bovine leukemia virus DNA in their breast tissue. So this is clear evidence that around one third of the human population at least is infected with the BLV retrovirus.
These US and Australian studies respectively found that 59% and 81% of women with breast cancer had BLV in their breast tissues, thus suggesting bovine leukemia virus may play a role in breast cancer. Although a study which sequenced the genome of some breast cancers found no evidence of BLV DNA in these tumors, which argues against the link between BLV and human breast cancer. And a study found that those who drank raw milk (were BLV is found) did not have a higher rate of cancer (but remember that BLV is already present in many humans, so then drinking raw milk provides no extra risk). At present the jury is still out regarding whether BLV can cause breast cancer.
A Possible Role for Bovine Leukemia Virus in ME/CFS?
What we are going to consider here is whether bovine leukemia virus infection in humans may have immunosuppressive effects that play a role ME/CFS. In particular, we can ask the question whether a possible immune suppression from a human BLV infection might explain why many ME/CFS patients have chronic active enterovirus or herpesvirus infections that they cannot seem to clear or keep under control?
Many doctors and researchers believe these chronically active enterovirus and herpesvirus of ME/CFS may be the cause of the disease. Could the immunosuppressive bovine leukemia virus be the hidden enabling factor behind these chronic enterovirus or herpesvirus infections? Could BLV be the reason ME/CFS patients cannot clear enterovirus or herpesvirus from their tissues, and thus cannot recover from ME/CFS? This is what we consider in the next section.
The Immunosuppressive Effects of Bovine Leukemia Virus
Bovine leukemia virus (which is also called bovine leukosis virus) is known to cause various forms of immune suppression in cows, which are as follows.
One study found that in cows, BLV induces TGF‐beta secretion from regulatory T cells (TGF‐beta in turn was found to suppress the secretion of the antiviral Th1 cytokines interferon gamma and TNF-alpha by CD4 T cells, as well as suppress natural killer cell cytotoxicity). This may allow opportunistic infections to arise.
Interestingly, we know that TGF‐beta is high in ME/CFS (this is one of the most consistent cytokine findings in ME/CFS). So that is in keeping with what BLV infection does in cows.
Another study found that in cows, BLV infection decreased secretory IgM and decreased T-cells in the blood (mainly CD4 T-cells). And a correlation was found between BLV infection and lack of spontaneous recovery from Trichophyton verrucosum (ringworm fungus) infection, indicating an immunosuppressive effect of BLV in cows. The study also notes that other BLV studies have found significant association between herd BLV infection status and disease incidence in the herd.
This study also details the B-cell and T-cell abnormalities found in cows positive for BLV. The study notes that BLV infection also negatively affects the functioning of monocytes and macrophages.
This article states that in cows, the primary cellular target of BLV infection is B-cells. Once infected with the virus, B-cell populations increase due to abnormal growth, resulting in a persistent lymphocytosis and eventually lymphomas (cancer of the lymphatic system) in cows.
BLV is closely related to the human retrovirus virus HTLV-1, and certainly in the case of human HTLV-1 infection, case studies of opportunistic infections with cytomegalovirus and herpes zoster have been reported.
So could the above immunological abnormalities found in cows explain the fact that the immune system of human ME/CFS patients seems to have trouble keeping enteroviruses and herpesviruses under control?
Well, we don't know if BLV causes in humans the same immunosuppressive effects in creates in cattle, and even if it did, the mechanism by which these effects might lead to chronic enteroviruses and herpesviruses infections is not clear. But it seems within the realm of possibility that BLV may be playing an immunosuppressive role in ME/CFS.
But it's just guessing at this stage, as very little is known about what bovine leukemia virus does in humans, because we only recently discovered this cow virus could infect humans.
How is Bovine Leukemia Virus Transmitted to Humans?
How do humans get infected with BLV? The Australian study says:
Bovine leukemia virus is present in raw unpasteurized milk, so it is possible this virus passed into human populations millennia ago, in an era long before pasteurization of milk was introduced, and is now transmitted from human to human. The human practice of drinking another animals' milk, which became common after the agricultural revolution 10,000 year ago, could have first introduced this cow virus into human populations.
And/or it is possible that humans are even today catching BLV directly from cows by consuming unpasteurized dairy or undercooked beef. At this stage we don't know how the virus gets into humans. (A study on people who consume raw milk found no increased incidence of breast cancer, though.)
Antivirals for Bovine Leukemia Virus?
Bovine leukemia virus falls within the deltaretrovirus genus. This contrasts to murine leukemia virus (MLV), feline leukemia virus (FLV) and XMRV which are from the gammaretrovirus genus.
Bovine leukemia virus is closely related to the human retrovirus virus called human T-lymphotropic virus 1 (HTLV-1), which is also found in the same deltaretrovirus genus.
Raltegravir has been shown to inhibit FLV, and also shown to inhibit MLV. Tenofovir has been shown to inhibit FLV. Elvitegravir has been shown to inhibit gammaretroviruses.
However, whether any of these antiretroviral drugs would work for BLV, I don't know. In a study on Raltegravir for HTLV-1 (the closest virus to BLV), there was little effect, with the authors noting that "lack of continuous viral replication cycles in chronic HTLV-1 carriers most likely explains our findings."
Some new research has shown that an anti-PD-1 antibody drug can reactivate the suppressed immune cells caused by BLV infection, and as the immune response is revitalized in this way, it leads to a decrease in BLV viral loads in cows.
Any Evidence for Bovine Leukemia Virus in ME/CFS?
Professor Ian Lipkin's high throughput sequencing study found retroviruses in 85% of ME/CFS patients' blood plasma samples, so this I think would be consistent with bovine leukemia virus playing a role in ME/CFS.
Dr Judy Mikovits detected gammaretrovirus proteins in ME/CFS, as well as anti-gammaretrovirus Env antibodies. I think we can confident that her XMRV findings were incorrect and due to contamination, but whether these gammaretrovirus findings still hold is another question. However, I am not sure if this offers evidence for BLV in ME/CFS, as BLV is a deltaretrovirus, not a gammaretrovirus.
Dr Elaine Defreitas found a HTLV-II-like retrovirus in ME/CFS patients, but most people could not replicate her findings, including Defreitas herself. But interestingly, HTLV-I and HTLV-II are very similar to BLV, so this makes you wonder whether the virus similar to HTLV-II that Defreitas found in ME/CFS patients might have been BLV.
An article on Defreitas's discovery of this HTLV-II-like can be found here: part 1 and part 2.
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