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Trehalose Inhibits Cytomegalovirus Infection in Multiple Cell Types

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  • Russell Farris
    I was working for several years on a book about the inter-relatedness of chronic diseases. I accumulated such a large database of examples that I had to use a
    Message 1 of 6 , Jun 16, 2017
      I was working for several years on a book about the inter-relatedness of chronic diseases. I accumulated such a large database of examples that I had to use a database management program--Access--to make sense of it all. I wasn't sure how to put all of the data in a book. I thought about adding a disk to the book.
              Soon after I moved to Roseville in 2014 I was struck down with levothyroxine poisoning and I took such a heavy hit cognitively that I had to give up on the project. There is an early rough draft of the book at: http://www.polymicrobial.com/.  I can still get data out of the database, and one of the pieces of data is the fact the that the human herpes virus cytomegalovirus (HCMV) has been linked to 180 different disorders. In most cases it is a cofactor, but it is the sole or main cause of many common disorders. HCMV infects nearly everyone. It is of particular interest to us old timers because it is the main cause of immunosenescence.
              The abstract below describes an in vitro experiment were human cells were infected with HCMV. Some of the cells were treated with trehalose, and the trehalose-treated cells were more resistant to infection. Could some of the benefits I'm getting from trehalose be due to inhibition of HCMV? Inquiring minds are waiting to find out. :-) Russ
      ================
       
      J Virol. 2015 Nov 11;90(3):1259-77. doi: 10.1128/JVI.02651-15.

      Trehalose, an mTOR-Independent Inducer of Autophagy, Inhibits Human Cytomegalovirus Infection in Multiple Cell Types.

      Abstract

      Human cytomegalovirus (HCMV) is the major viral cause of birth defects and a serious problem in immunocompromised individuals and has been associated with atherosclerosis. Previous studies have shown that the induction of autophagy can inhibit the replication of several different types of DNA and RNA viruses. The goal of the work presented here was to determine whether constitutive activation of autophagy would also block replication of HCMV. Most prior studies have used agents that induce autophagy via inhibition of the mTOR pathway. However, since HCMV infection alters the sensitivity of mTOR kinase-containing complexes to inhibitors, we sought an alternative method of inducing autophagy. We chose to use trehalose, a nontoxic naturally occurring disaccharide that is found in plants, insects, microorganisms, and invertebrates but not in mammals and that induces autophagy by an mTOR-independent mechanism. Given the many different cell targets of HCMV, we proceeded to determine whether trehalose would inhibit HCMV infection in human fibroblasts, aortic artery endothelial cells, and neural cells derived from human embryonic stem cells. We found that in all of these cell types, trehalose induces autophagy and inhibits HCMV gene expression and production of cell-free virus. Treatment of HCMV-infected neural cells with trehalose also inhibited production of cell-associated virus and partially blocked the reduction in neurite growth and cytomegaly. These results suggest that activation of autophagy by the natural sugar trehalose or other safe mTOR-independent agents might provide a novel therapeutic approach for treating HCMV disease.

      IMPORTANCE:

      HCMV infects multiple cell types in vivo, establishes lifelong persistence in the host, and can cause serious health problems for fetuses and immunocompromised individuals. HCMV, like all other persistent pathogens, has to finely tune its interplay with the host cellular machinery to replicate efficiently and evade detection by the immune system. In this study, we investigated whether modulation of autophagy, a host pathway necessary for the recycling of nutrients and removal of protein aggregates, misfolded proteins, and pathogens, could be used to target HCMV. We found that autophagy could be significantly increased by treatment with the nontoxic, natural disaccharide trehalose. Importantly, trehalose had a profound inhibitory effect on viral gene expression and strongly impaired viral spread. These data constitute a proof-of-concept for the use of natural products targeting host pathways rather than the virus itself, thus reducing the risk of the development of resistance to treatment.

    • Paula Carnes
      How much trehalose are you ingesting a day? I looked it up and noticed it is made from corn - not something good for me to eat. It is one of a few things I
      Message 2 of 6 , Jun 17, 2017
        How much trehalose are you ingesting a day? I looked it up and noticed it is made from corn - not something good for me to eat. It is one of a few things I seem to have an allergic reaction to. 

        I just started using mannitol for sugar. No idea if any of this stuff makes any difference.

        Paula Carnes


        On Jun 16, 2017, at 5:41 PM, 'Russell Farris' russ@... [infection-cortisol] <infection-cortisol@yahoogroups.com> wrote:


        I was working for several years on a book about the inter-relatedness of chronic diseases. I accumulated such a large database of examples that I had to use a database management program--Access--to make sense of it all. I wasn't sure how to put all of the data in a book. I thought about adding a disk to the book.
                Soon after I moved to Roseville in 2014 I was struck down with levothyroxine poisoning and I took such a heavy hit cognitively that I had to give up on the project. There is an early rough draft of the book at: http://www.polymicrobial.com/.  I can still get data out of the database, and one of the pieces of data is the fact the that the human herpes virus cytomegalovirus (HCMV) has been linked to 180 different disorders. In most cases it is a cofactor, but it is the sole or main cause of many common disorders. HCMV infects nearly everyone. It is of particular interest to us old timers because it is the main cause of immunosenescence.
                The abstract below describes an in vitro experiment were human cells were infected with HCMV. Some of the cells were treated with trehalose, and the trehalose-treated cells were more resistant to infection. Could some of the benefits I'm getting from trehalose be due to inhibition of HCMV? Inquiring minds are waiting to find out. :-) Russ
        ================
         
        J Virol. 2015 Nov 11;90(3):1259-77. doi: 10.1128/JVI.02651-15.

        Trehalose, an mTOR-Independent Inducer of Autophagy, Inhibits HumanCytomegalovirus Infection in Multiple Cell Types.

        Abstract

        Human cytomegalovirus (HCMV) is the major viral cause of birth defects and a serious problem in immunocompromised individuals and has been associated with atherosclerosis. Previous studies have shown that the induction of autophagy can inhibit the replication of several different types of DNA and RNA viruses. The goal of the work presented here was to determine whether constitutive activation of autophagy would also block replication of HCMV. Most prior studies have used agents that induce autophagy via inhibition of the mTOR pathway. However, since HCMV infection alters the sensitivity of mTOR kinase-containing complexes to inhibitors, we sought an alternative method of inducing autophagy. We chose to use trehalose, a nontoxic naturally occurring disaccharide that is found in plants, insects, microorganisms, and invertebrates but not in mammals and that induces autophagy by an mTOR-inde pendent mechanism. Given the many different cell targets of HCMV, we proceeded to determine whether trehalose would inhibit HCMV infection in human fibroblasts, aortic artery endothelial cells, and neural cells derived from human embryonic stem cells. We found that in all of these cell types, trehalose induces autophagy and inhibits HCMV gene expression and production of cell-free virus. Treatment of HCMV-infected neural cells with trehalose also inhibited production of cell-associated virus and partially blocked the reduction in neurite growth and cytomegaly. These results suggest that activation of autophagy by the natural sugar trehalose or other safe mTOR-independent agents might provide a novel therapeutic approach for treating HCMV disease.

        IMPORTANCE:

        HCMV infects multiple cell types in vivo, establishes lifelong persistence in the host, and can cause serious health problems for fetuses and immunocompromised individuals. HCMV, like all other persistent pathogens, has to finely tune its interplay with the host cellular machinery to replicate efficiently and evade detection by the immune system. In this study, we investigated whether modulation of autophagy, a host pathway necessary for the recycling of nutrients and removal of protein aggregates, misfolded proteins, and pathogens, could be used to target HCMV. We found that autophagy could be significantly increased by treatment with the nontoxic, natural disaccharide trehalose. Importantly, trehalose had a profound inhibitory effect on viral gene expression and strongly impaired viral spread. These data constitute a proof-of-concept for the use of natural produ cts targeting host pathways rather than the virus itself, thus reducing the risk of the development of resistance to treatment.



      • Evan Jones
        Russ quotes a study which found that : Some of the cells [infected with herpes virus cytomegalovirus (HCMV)] were treated with trehalose, and the
        Message 3 of 6 , Jun 17, 2017
          Russ quotes a study which found that :

          "Some of the cells [infected with herpes virus cytomegalovirus (HCMV)]
          were treated with
          trehalose, and the trehalose-treated cells were more resistant to infection."

          My first thought was to see if there is similarity between trelahose
          and the sugar d-ribose - but there is nothing much, it seems.

          One of the oldest traditional Chinese medicines, said to have been in
          use for 5,000 years, is the once rare and not very pleasant tasting
          woody mushroom called Reishi (Ganoderma Lucidium). TCM claims a very
          wide range of health benefits [which I wont bother to repeat here, as
          there is plenty of info about "Reishi" on the internet.]

          Ray Peat advises eating plenty of mushrooms, some of which have as
          much as 18% trehalose by dry weight.
          https://en.wikipedia.org/wiki/Trehalose#Biological_properties

          The same Wiki article also says:
          "It is also said[by whom?] that the reason dried shiitake mushrooms
          spring back into shape so well in water is because they contain
          trehalose."

          The brilliant young Ray Peat acolyte who calls himself Haidut, says of
          trelhalose:
          "Ray wrote in one of his recent newsletters about mushrooms and their
          beneficial effects on human health (if well cooked). In particular, he
          wrote about the sugar trehalose found exclusively in mushrooms and how
          it stabilizes the cells of the animals that eat it. This study now
          says that eating the human equivalent of about 20g - 25g trehalose
          daily can not only reverse fatty liver disease but also lead to weight
          loss. This amount of trehalose is easily achievable by eating about
          3-4 ounces of muchrooms."

          The rest of the discussion at this link contains a lot of of other
          interesting info:
          https://raypeatforum.com/community/threads/fungal-sugar-trehalose-may-treat-fatty-liver-disease.9857/
        • Russell Farris
          Hi Paula, In eight days I have used about a quarter of a pound of Swanson-brand trehalose. I use a small spoon and the spoon half-full holds as much as I can
          Message 4 of 6 , Jun 17, 2017
            Hi Paula,
            In eight days I have used about a quarter of a pound of Swanson-brand trehalose. I use a small spoon and the spoon half-full holds as much as I can put under my tongue. I take some before naps and at bed time. If I wake up in the middle of the night I take some. I take it after every meal. I take some when I feel pain or I feel tired. I've had a stuffy nose for seventy years; trehalose opens my nose up and allows me to breathe easily in about 15 minutes. It also clears up my COPD symptoms for a couple of hours.
                    I have no idea what the optimum dose is--I'm just feeling my way.
                    Trehalose is also called mushroom sugar, but I guess it is cheaper to synthesize it from corn than to extract it from mushrooms. I have no idea what it will do to your corn allergies. Evan says that dried mushrooms are as much as 18% trehalose. Are you allergic to mushrooms?
                    In the video by Dr. Phillips, he mentions a lot of other autophagy-inducers. I started with trehalose because it is cheap and readily available. I'm too new to this whole field of study to know whether it is the best.
                    Good luck. Russ
             
            ------ Original Message ------
            From: "Paula"
            Sent: 6/17/2017 1:49:02 PM
            Subject: Re: [infection-cortisol] Trehalose Inhibits Cytomegalovirus Infection in Multiple Cell Types

            How much trehalose are you ingesting a day? I looked it up and noticed it is made from corn - not something good for me to eat. It is one of a few things I seem to have an allergic reaction to. 

            I just started using mannitol for sugar. No idea if any of this stuff makes any difference.

            Paula Carnes


            On Jun 16, 2017, at 5:41 PM, 'Russell Farris' russ@... [infection-cortisol] <infection-cortisol@yahoogroups.com> wrote:


            I was working for several years on a book about the inter-relatedness of chronic diseases. I accumulated such a large database of examples that I had to use a database management program--Access--to make sense of it all. I wasn't sure how to put all of the data in a book. I thought about adding a disk to the book.
                    Soon after I moved to Roseville in 2014 I was struck down with levothyroxine poisoning and I took such a heavy hit cognitively that I had to give up on the project. There is an early rough draft of the book at: http://www.polymicrobial.com/.  I can still get data out of the database, and one of the pieces of data is the fact the that the human herpes virus cytomegalovirus (HCMV) has been linked to 180 different disorders. In most cases it is a cofactor, but it is the sole or main cause of many common disorders. HCMV infects nearly everyone. It is of particular interest to us old timers because it is the main cause of immunosenescence.
                    The abstract below describes an in vitro experiment were human cells were infected with HCMV. Some of the cells were treated with trehalose, and the trehalose-treated cells were more resistant to infection. Could some of the benefits I'm getting from trehalose be due to inhibition of HCMV? Inquiring minds are waiting to find out. :-) Russ
            ================
             
            J Virol. 2015 Nov 11;90(3):1259-77. doi: 10.1128/JVI.02651-15.

            Trehalose, an mTOR-Independent Inducer of Autophagy, Inhibits HumanCytomegalovirus Infection in Multiple Cell Types.

            Abstract

            Human cytomegalovirus (HCMV) is the major viral cause of birth defects and a serious problem in immunocompromised individuals and has been associated with atherosclerosis. Previous studies have shown that the induction of autophagy can inhibit the replication of several different types of DNA and RNA viruses. The goal of the work presented here was to determine whether constitutive activation of autophagy would also block replication of HCMV. Most prior studies have used agents that induce autophagy via inhibition of the mTOR pathway. However, since HCMV infection alters the sensitivity of mTOR kinase-containing complexes to inhibitors, we sought an alternative method of inducing autophagy. We chose to use trehalose, a nontoxic naturally occurring disaccharide that is found in plants, insects, microorganisms, and invertebrates but not in mammals and that induces autophagy by an mTOR-inde pendent mechanism. Given the many different cell targets of HCMV, we proceeded to determine whether trehalose would inhibit HCMV infection in human fibroblasts, aortic artery endothelial cells, and neural cells derived from human embryonic stem cells. We found that in all of these cell types, trehalose induces autophagy and inhibits HCMV gene expression and production of cell-free virus. Treatment of HCMV-infected neural cells with trehalose also inhibited production of cell-associated virus and partially blocked the reduction in neurite growth and cytomegaly. These results suggest that activation of autophagy by the natural sugar trehalose or other safe mTOR-independent agents might provide a novel therapeutic approach for treating HCMV disease.

            IMPORTANCE:

            HCMV infects multiple cell types in vivo, establishes lifelong persistence in the host, and can cause serious health problems for fetuses and immunocompromised individuals. HCMV, like all other persistent pathogens, has to finely tune its interplay with the host cellular machinery to replicate efficiently and evade detection by the immune system. In this study, we investigated whether modulation of autophagy, a host pathway necessary for the recycling of nutrients and removal of protein aggregates, misfolded proteins, and pathogens, could be used to target HCMV. We found that autophagy could be significantly increased by treatment with the nontoxic, natural disaccharide trehalose. Importantly, trehalose had a profound inhibitory effect on viral gene expression and strongly impaired viral spread. These data constitute a proof-of-concept for the use of natural produ cts targeting host pathways rather than the virus itself, thus reducing the risk of the development of resistance to treatment.


          • Russell Farris
            Thanks, Evan, for the info on the trehalose in mushrooms. I like mushrooms, but I have always been afraid of them. Russ ... From: Evan To:
            Message 5 of 6 , Jun 17, 2017
               Thanks, Evan, for the info on the trehalose in mushrooms. I like mushrooms, but I have always been afraid of them. Russ
               
              ------ Original Message ------
              From: "Evan"
              Cc: "the-free-thinkers-email" <the-free-thinkers-email@...>
              Sent: 6/17/2017 6:28:40 PM
              Subject: [infection-cortisol] Re: Trehalose Inhibits Cytomegalovirus Infection in Multiple Cell Types
               
              Russ quotes a study which found that :
               
              "Some of the cells [infected with herpes virus cytomegalovirus (HCMV)]
              were treated with
              trehalose, and the trehalose-treated cells were more resistant to infection."
               
              My first thought was to see if there is similarity between trelahose
              and the sugar d-ribose - but there is nothing much, it seems.
               
              One of the oldest traditional Chinese medicines, said to have been in
              use for 5,000 years, is the once rare and not very pleasant tasting
              woody mushroom called Reishi (Ganoderma Lucidium). TCM claims a very
              wide range of health benefits [which I wont bother to repeat here, as
              there is plenty of info about "Reishi" on the internet.]
               
              Ray Peat advises eating plenty of mushrooms, some of which have as
              much as 18% trehalose by dry weight.
               
              The same Wiki article also says:
              "It is also said[by whom?] that the reason dried shiitake mushrooms
              spring back into shape so well in water is because they contain
              trehalose."
               
              The brilliant young Ray Peat acolyte who calls himself Haidut, says of
              trelhalose:
              "Ray wrote in one of his recent newsletters about mushrooms and their
              beneficial effects on human health (if well cooked). In particular, he
              wrote about the sugar trehalose found exclusively in mushrooms and how
              it stabilizes the cells of the animals that eat it. This study now
              says that eating the human equivalent of about 20g - 25g trehalose
              daily can not only reverse fatty liver disease but also lead to weight
              loss. This amount of trehalose is easily achievable by eating about
              3-4 ounces of muchrooms."
               
              The rest of the discussion at this link contains a lot of of other
              interesting info:
               
               
            • Russell Farris
              Thanks, Evan, for all of the information on trehalose in muchrooms. I like mushrooms, but I have always been afraid of them. Russ ... From: Evan To:
              Message 6 of 6 , Jun 22, 2017
                 Thanks, Evan, for all of the information on trehalose in muchrooms. I like mushrooms, but I have always been afraid of them. Russ
                 
                ------ Original Message ------
                From: "Evan"
                Cc: "the-free-thinkers-email" <the-free-thinkers-email@...>
                Sent: 6/17/2017 6:28:40 PM
                Subject: [infection-cortisol] Re: Trehalose Inhibits Cytomegalovirus Infection in Multiple Cell Types
                 
                Russ quotes a study which found that :
                 
                "Some of the cells [infected with herpes virus cytomegalovirus (HCMV)]
                were treated with
                trehalose, and the trehalose-treated cells were more resistant to infection."
                 
                My first thought was to see if there is similarity between trelahose
                and the sugar d-ribose - but there is nothing much, it seems.
                 
                One of the oldest traditional Chinese medicines, said to have been in
                use for 5,000 years, is the once rare and not very pleasant tasting
                woody mushroom called Reishi (Ganoderma Lucidium). TCM claims a very
                wide range of health benefits [which I wont bother to repeat here, as
                there is plenty of info about "Reishi" on the internet.]
                 
                Ray Peat advises eating plenty of mushrooms, some of which have as
                much as 18% trehalose by dry weight.
                 
                The same Wiki article also says:
                "It is also said[by whom?] that the reason dried shiitake mushrooms
                spring back into shape so well in water is because they contain
                trehalose."
                 
                The brilliant young Ray Peat acolyte who calls himself Haidut, says of
                trelhalose:
                "Ray wrote in one of his recent newsletters about mushrooms and their
                beneficial effects on human health (if well cooked). In particular, he
                wrote about the sugar trehalose found exclusively in mushrooms and how
                it stabilizes the cells of the animals that eat it. This study now
                says that eating the human equivalent of about 20g - 25g trehalose
                daily can not only reverse fatty liver disease but also lead to weight
                loss. This amount of trehalose is easily achievable by eating about
                3-4 ounces of muchrooms."
                 
                The rest of the discussion at this link contains a lot of of other
                interesting info:
                 
                 
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