Study Connects Herpes to Biological Risk for Alzheimer’s
A biological framework called the “microcompetition model” may explain why people infected with herpes simplex 1 (HSV1) are at increased risk of developing Alzheimer’s disease.
“These dynamics explain the observed connection reported in many studies between the virus and Alzheimer’s disease, and provide a framework for further investigations,” researchers wrote.
This idea was outlined in the paper, “How an increase in the copy number of HSV-1 during latency can cause Alzheimer’s disease: the viral and cellular dynamics according to the microcompetition model,” published in the Journal of NeuroVirology.
HSV1 infection can cause genital herpes, though it more commonly causes sores around the mouth and lips (sometimes called fever blisters or cold sores). Emerging data has suggested that people who are infected with HSV1 are at increased risk of developing Alzheimer’s. However, it’s unclear what biological phenomena might be responsible for this connection.
Now, a pair of scientists at the Center for the Biology of Chronic Disease in the U.S. have proposed a possible mechanism. In their paper, the team’s goal was “to connect seemingly unconnected observations reported in the literature to build the molecular dynamics that lead from” HSV1 infection to Alzheimer’s, they wrote.
At times, HSV1 infections can be lytic; that’s when sores appear. However, most of the time, HSV1 infections are latent; essentially, the virus lingers in nerve cells without causing overt damage. The researchers think this phase of viral infection is mainly responsible for the link to Alzheimer’s.
Although HSV1 doesn’t really cause overt damage in the latency phase, the virus is still active. In other words, its DNA is being constantly “read” in infected cells.
When a cell “reads” a gene, the process requires certain proteins called transcription factors, which bind to the cell’s DNA and help to coordinate the “reading.” When a cell “reads” a viral gene, it also requires transcription factors, including some of the same proteins needed to read the cell’s own DNA.
This is the basis of the microcompetition model: When a cell is infected with HSV1 during latency, some of the cell’s transcription factors are being used to “read” the viral genes. Since the amount of transcription factors in the cell doesn’t change in response to infection, this necessarily means that the amount of transcription factors the cell has available for its own normal processes is reduced.
In their paper, the researchers specifically highlight that certain transcription factors — particularly one called GABP — are used to “read” certain HSV1 genes during latent infection.
Reduced levels of these transcription factors in cells are known to disrupt autophagy — a process that cells use to “recycle” complex molecules — as well as the function of mitochondria, the so-called powerhouses of cells. These transcription factors also are important for maintaining the health of nerve cells.
Disrupted autophagy and mitochondrial function, as well as impaired nerve health, are well-established biological hallmarks of Alzheimer’s.
Notably, the researchers said that the microcompetition model also may explain why not everyone infected with HSV1 develops Alzheimer’s. Basically, the researchers think the difference may have to do with the amount of HSV1 DNA in cells, referred to as the virus copy number. In people with more HSV1 DNA (a higher copy number), there will be greater competition for transcription factors, and therefore an increased risk of Alzheimer’s.
“Since the current understanding of the dynamics and homeostasis of the viral reservoir during latency is limited, the proposed model represents only a first step toward a complete understanding of the relationship between the copy number of the latent HSV-1 and Alzheimer’s disease,” the researchers wrote, stressing a need for more research in this area.
“We highly recommend considering using anti-viral agents that target the latent HSV-1 as a preventive treatment” for Alzheimer’s, the team added.
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