Viral Reactivation Models

Periodic reactivation of latent herpesviruses (EBV, HHV-6, CMV) has been implicated in ME/CFS symptom exacerbation. Viral reactivation is inherently stochastic: the switch from latent to lytic infection is a rare event governed by small numbers of viral transcription factors. The model uses a stochastic framework (master equation) for the latent–lytic transition and deterministic ODEs for the subsequent immune response.

The viral load \(V\) follows:

\[ \frac{d V}{d t} = r_V \cdot V \cdot (1 - \frac{V}{V_{\text{max}}}) - k_{\text{clear}} \cdot N_a \cdot V - k_{\text{CTL}} \cdot T_e^{\text{CD8}} \cdot V \tag{1}\]

where \(r_V\) is the viral replication rate, \(k_{\text{clear}}\) is the NK-mediated clearance rate, and \(k_{\text{CTL}}\) is the cytotoxic T lymphocyte (CTL) killing rate. The latent-to-lytic transition is modeled as a Poisson process with rate \(\lambda_{\text{react}}\) that increases under conditions of immune suppression, metabolic stress, or elevated cortisol:

\[ \lambda_{\text{react}} = \lambda_0 \cdot \frac{K_{\text{immune}}}{K_{\text{immune}} + N_a + T_e^{\text{CD8}}} \cdot (1 + \alpha_{\text{stress}} \cdot [\text{Cortisol}]) \tag{2}\]

The model predicts that the reduced NK cell activity and T cell exhaustion characteristic of ME/CFS increase the reactivation rate \(\lambda_{\text{react}}\), producing more frequent viral flares that further stimulate the immune system—a positive feedback loop between immune dysfunction and viral persistence. EBV-specific findings, including recent evidence of EBV-driven demyelination mechanisms (Pless et al. 2026), suggest that viral reactivation may have tissue-specific consequences beyond generalized immune stimulation.

References

Pless, Annika et al. 2026. “Myelin Antigen Capture in the CNS by B Cells Expressing EBV Latent Membrane Protein 1 Leads to Demyelinating Lesion Formation.” Cell. https://doi.org/10.1016/j.cell.2025.12.031.