Mixed CMV infections have been linked to high viral loads and worse prognosis in transplant patients. A team of Japanese investigators led by Tetsushi Yoshikawa found evidence of mixed infections of human herpesvirus 6B (HHV-6B) in two out of 15 stem cell transplant patients. Furthermore, in two patients the strain in the spinal fluid differed from that in the peripheral blood, suggesting compartmentalization of HHV-6 reactivation. In other words, the HHV-6B virus that reactivated in the brain tissues was not the same as the strain that activated in the periphery.
The investigators utilized a novel approach to characterize the strains. The analysis was done by quantifying the copy numbers of telomeric repeat sequences (TRS) among various clinical isolates in immunocompetent and immunocompromised individuals. These repeat sequences are located at the ends of the HHV-6 genome and vary considerably by strain. The investigators then compared telomeric sequences in clinical isolates obtained from exanthem subitum cases to those from patients with DIHS and post-transplant reactivation. The sizes of the telomeric sequences in each strain differ considerably, making it possible to determine the number of variants without isolating each strain individually. While most of the patients had the same strain reactivating, two transplant patients had infections of multiple strains. In one case, a spinal fluid and peripheral blood had two different strains. However, after neurological symptoms worsened, the CNS strain was found in the periphery as well.
CMV studies have suggested that both the number of strains active and specific genotypes may have an impact on the clinical course in CMV disease. In one study, of CMV in immunocompromised patients, patients with multiple infections progressed to CMV disease while those with single strain infections did not (Coaquette 2004). The authors noted that the specific telomeric repeat ‘signature’ of each strain remained stable, even after multiple generations or passages. Taken together, these results suggest that PCR analysis of TRS copy number is a reliable tool for determining the number of isolates present in a sample, which in turn may have important clinical relevance in several clinical contexts of HHV-6B infection. The authors suggest further studies to analyze the compartmentalization of HHV-6B strains in the CNS and periphery.
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