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A link between EBV and LPS? (and other Toll Like receptors microbial activators)


Senior Member
The influence of toll-like receptor stimulation on expression of EBV lytic genes. (free access)
Epstein-Barr virus (EBV) establishes latency in the resting memory B-cell compartment. It has been recently suggested that maintenance of chronic infection is dependent on periodic reactivation. Although the stimuli for EBV reactivation in vivo during natural infections are largely unknown, there is evidence indicating that heterologous infections could trigger herpesviruses reactivation. The purpose of this work was to identify the influence of Toll-like receptors stimulation on EBV replication in EBV latently infected Burkitt lymphoma cells (P3HR-1, Raji and Namalwa).
The cells were stimulated with Pam3CSK4 (synthetic triacylated lipoprotein), PolyI:C (synthetic analog of dsRNA), LPS (lipopolysaccharide from E.coli), measles virus (MeV) and PMA (phorbol myristate acetate).
Non-stimulated cells (NS) served as control.
EBV expression was investigated at mRNA level for three viral lytic genes: BZLF1 (immediate early, ZEBRA), BALF2 (early, EA) and BcLF1 (late, VCA).
Additionally, the effect of stimulation on NF-kBp65 and inflammatory cytokines (IL-lb, IL-6, IL-8, IL-10, IL-12p70, and TNF) was investigated.
Stimulation of TLRs led to limited changes in EBV expression manifesting as increase of ZEBRA at mRNA level in cells treated with PolyI:C and Pam3CSK4.
Stimulation with PolyI:C, Pam3CSK4 and LPS also lead to considerable increase of NF-kBp65, while increased levels of inflammatory cytokines were observed for IL-8, TNF and IL-6 in cells treated with PMA and MeV.
In conclusion, the results of our experiments support the suggestion that TLRs stimulation with microbial ligands influences EBV virus replication

from Wiki,
Polyl C activates TLR3 (polyl C = double strand RNA from viruses)
LPS activates TLR4 (LPS is from Escherichia Coli from the gut, but also from Chlamydia)
Triacylated lipoprotein activates TLR10, TLR2 (lipoprotein are from both gram+ and - bacteria)
Heat Shock Protein 10 of Chlam Pneumoniae activates TLR2 and TLR4
Mycoplasma Pneumo + Chlam Pneumo is linked to activation of TLR2 + TLR4

Another scientific paper on the same topic:

Toll-Like Receptor Agonists Synergistically Increase Proliferation and Activation of B Cells by Epstein-Barr Virus

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Senior Member

What do you think of this study?

They investigated three lytic EBV antigens (EA, ZEBRA, VCA) in response to stimulation of different TLR.

It seems to me that activation of TLR3 and TLR10 by microbial agents increase ZEBRA
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Senior Member
I am not sure if I can see any immediate significance of this study for ME/CFS.

TLR-3 is the receptor that normally responds to the presence of viral dsRNA in the cell. If TLR-3 senses dsRNA, it releases interferons.

TLR-4 responds to LPS.

Since enterovirus, EBV and HHV-6 are all known to infect B-cells (see this thread), and since chronic non-cytolytic enterovirus infections in cells constantly produce low levels of enteroviral dsRNA, I guess if a B-cell was co-infected with both enterovirus and EBV, then perhaps the enterovirus dsRNA might trigger these EBV lytic antigens.

There was one study that suggested some subtypes of ME/CFS may be due to partial reactivation of Epstein-Barr virus. Refs: 1 2

There are actually 3 latency states of EBV. In the deepest state of latency (latency I) no viral proteins are produced; but in the two states of latency (latency I and III), although the virus is still not fully reactivated, some EBV viral proteins are produced. In B-cells, all 3 states of latency are possible.
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