Human Herpesvirus 6 and 7 Reactivation and Disease Activity in Multiple Sclerosis

Abstract

Recent studies have focused on the associations between human herpesvirus 6 (HHV-6) and human herpesvirus 7 (HHV-7), and multiple sclerosis (MS). The aim of this study was to investigate the associations between HHV-6 and HHV-7 reactivation and MS disease activity, and interleukin 12 (IL-12) and tumor necrosis factor α (TNF-α) production. Material and Methods. The frequency of plasma viremia by nested polymerase chain reaction and transcription of viral mRNA in peripheral blood mononuclear cells by reverse transcriptasepolymerase chain reaction (RT-PCR) of 14 relapsing/remitting (RR) and 14 secondary progressive (SP) MS patients were studied in comparison with clinical manifestation of the disease. Serum concentrations of cytokines IL-12 and TNF-α were analyzed by enzyme-linked immunosorbent assay. Results. Plasma samples from 25 of the 28 MS patients with estimated latent/persistent HHV-6 and/or HHV-7 infection were examined during relapse and remission/relative remission. HHV-6 reactivation was found in 4 of the 7 RRMS and 4 of the 7 SPMS patients, and HHV-7 reactivation was identified in 3 of the 7 RRMS and 1 of the 7 SPMS patients (all in relapse). In 2 of the 3 RRMS patients without viremia in relapse, HHV-6 mRNA transcription was detected. In RRMS and SPMS patients with active HHV-6 and HHV-7 infection in relapse, the serum concentrations of IL-12 and TNF-α were significantly higher than in those with latent virus infection. Conclusions. HHV-6 and HHV-7 reactivation could be implicated in the exacerbation of MS via activation of Th1 lymphocyte subsets.

Evidence linking HHV-6 with multiple sclerosis: an update

“…Interestingly, the authors noted that IgG titers reached their highest value two weeks, and IgM titers one month, before relapse [28]. A 2011 study of a Latvian MS cohort reported HHV-6 DNA in the plasma of a majority of RRMS and SPMS patients during relapse, which was confirmed by enhancing MRI lesions, and correlated with higher serum concentrations of the inflammatory cytokines IL-12 and TNF-alpha relative to periods of remission [29]. These data agree with earlier studies of serum HHV-6 detection during relapse and add the observation of cytokine correlates, complementing a recent study suggesting that TNF-alpha may be predictive of HHV-6 reactivation [30].…”

Cytokines and MMP-9 Levels in Rheumatoid Arthritis and Osteoarthritis Patients with Persistent Parvovirus B19, HHV-6 and HHV-7 Infection

“…Two-thirds of RA patients have been observed to be positive for HLA-DR * 4 (Colmegna and Alberts-Grill, 2009). The development of autoimmune diseases, including connective tissue diseases, multiple sclerosis and Hashimoto thyroiditis, has been associated with HHV-6 A/B infection (Chapenko et al, 2003;Nora-Krukle et al, 2011;Caselli et al, 2012;Hayem and Hayem, 2012;, Sultanova et al, 2017. It has been shown that several viral infections, including B19V, HHV-6 and HHV-7, may trigger the development and progression of arthritis.…”

Gerpes viruses and multiple sclerosis

“…Изучая признаки реактивации вируса у пациентов с РР РС и вторично прогрессирующим РС (ВП РС) с латентной инфекцией HHV-6 или HHV-7, Z. Nora-Krukle и соавт. [59] обнаружили накопление ДНК HHV-6 (и реже HHV-7) в сыворотке пациентов с РР и ВП РС, причем только в фазе обострения болезни. При этом у больных с реактивацией вируса сывороточные уровни цитокинов IL-12 и TNF-α значительно превышали показатели пациентов с латентной инфекцией.…”

“…Ряд сообщений свидетельствует в пользу предполагаемой роли HHV-6 в патогенезе РС. Например, установлена связь между обострением РС и реактивацией вируса, документированной накоплением анти-HHV-6 антител [57,58] или ДНК вируса в сыворотке крови [59,60].…”