Accidental discovery: obesity can prevent genital herpes in mice

To humans, herpes is often nothing more than a painful inconvenience, but for rodents, contracting this sexually transmitted disease is tantamount to a kiss
of death.
Injecting rats with human pathogens, such as herpes simplex virus (HSV), as is often done in laboratory studies, can kill them
within a few days.
But not all rodents are equally vulnerable
.
In a study published Nov.
8 in Cell Reports, researchers found that obese mice fed high-fat foods had a stronger immune response to HSV-2, which causes genital herpes
in humans, due to differences in their vaginal microbiota compared to thin mice.
This finding provides insights into the mechanisms behind the vaginal immune response and the role of the microbiome in fighting disease
.

Biomedical scientists have found that obesity in humans is associated
with a higher risk of cardiovascular disease, a higher risk of cancer, and in some cases a compromised immune system.
According to the study, although obesity is associated with a higher risk of cervical cancer mortality in women, scientists have not found any evidence of a link
between herpes and obesity.
Researchers at the Korea Advanced Institute of Science and Technology (KAIST), led by immunologist Heung Kyu Lee, want to test the effects of obesity on immunity against viruses, particularly genital herpes
, a common sexually transmitted infection in humans.
HSV-2 appeared later in human history than the more common HSV-1 type, which is known
for causing oral herpes.
More than 11% of people between the ages of 15 and 49 have genital herpes, but there is currently no cure
.
By comparing the immune responses of thin and obese female mice, the study authors wrote in the study that they hope to discover how obesity affects the immune response of the reproductive mucosa
.

The researchers fed some of the mice standard food and others high-fat food
to the rats.
They then infected all the mice with the HSV-2 virus and observed their immune response
within three weeks.
Scientists at the Korea Advanced Institute of Science and Technology wrote in the study that they expect it to increase susceptibility
to HSV-2.
To their surprise, they found that all the skinny rats died within the first two weeks, while half of the fat rats survived within three weeks
.
Obese mice also began clearing the virus
from their genital mucosa more quickly.

The scientists used flow cytometry to calculate the relative abundance of different cells in the mucosa and then compared the concentrations
in obese and thin mice.
They found that the vaginal mucosa of obese mice contained higher levels of cytotoxicity-δ (γδ) T cells, a type of white blood cell
that is very rare in the human body.
When the researchers used antibodies to inhibit the gamma delta T cell receptor, it significantly reduced the ability of obese mice to fight HSV-2 and had no effect on thin mice, suggesting that γδ T cells play a role
in the immunity of obese mice.

The team conducted a similar analysis of larger vaginal flora and found that removing vaginal commensal flora with antibiotics also significantly reduced survival in
obese mice.
The microbiota of obese mice differed from those of thin mice, with higher
levels of bacteria from the gut, such as E.
coli.
When the researchers introduced E.
coli into the vaginal microbiota of thin mice, they found that E.
coli promoted viral clearance and prevented HSV-2 symptoms
compared to controls.
Based on this information, the scientists hypothesized in their paper that obesity causes more bacteria from the gut to enter the reproductive tract, microbes that mitigate the lethal effects
of HSV-2 by controlling levels of gamma delta T cells and other immune cells.

Lorne Kastrukoff, a neuroscientist at the University of British Columbia, said: "It was surprising that they found that obesity actually affected viral infections
more positively.
" Lorne Kastrukoff had studied herpes in the past but was not involved in the new study
.

David Koelle, a translational immunologist at the University of Washington who was not involved in the study, agrees that it is a fascinating study, but he is "not sure how much it relates to humans" because the HSV-2 virus interacts with the body of mice differently than with humans
.
HSV-2 is a traditional human pathogen: Although there is still some debate about how and when HSV-2 is transmitted to humans, Koelle says it has co-evolved with us for at least 1 million years
.
In contrast, mice don't usually get infected with either of the human herpes variants, so their bodies react very differently
to it.
In humans, the virus stays at one site, and for HSV-2 the virus is usually the genital area
.
However, Koelle said, in mice, the virus traveled along the spinal cord into the brain, which is what
led to the animals' eventual death.

Kastrukoff added that the young age of the mice in the study (5 weeks), the type of HSV-2 and the strain of the mouse (C57BL/6 or "black 6," a common inbred line of laboratory mice) can all lead to atypical results
.
He explained that the immune system structure of black 6 mice is different from that of other lab mice, which may be responsible for
this effect.