Department of Microbiology, Royal Brompton Hospital, Imperial College School of Medicine, Sydney Street, London SW3 6NP and
1 University Department of Pathology, Western Infirmary, Glasgow G-11 6NT, UK
SIR, Chevrel and colleagues report the presence of parvovirus B19 DNA in muscle of a patient with dermatomyositis [1]. In 1997, we reported the similar detection of parvovirus B19 DNA in skeletal muscle of a case of mixed connective tissue disease and arthralgia [2]. This was not cited probably because the publication was in a journal not abstracted by Medline. The case, however, has interesting parallels.
Our patient was a 39-yr-old female with a 6-month history of disease. She had a weakly positive ANA titre of 256, but tested negative for other autoantibodies, including rheumatoid factors La, Ro, SMA, RNP and Jo-1. The parvovirus B19 strain was sequenced between nucleotides 1399 and 1682, and revealed 10 mutations compared with the published sequence [3]; nucleotide (nt) 1443, CT; nt 1455 C
T, nt 1466 G
C; nt 1476, A
G; nt 1482, C
T; nt 1491, C
T; nt 1506, C
T; nt 1554, A
G, nt 1602, C
A; nt 1611, C
A (GenBank accession no. 324452). This mutation rate of 3.52% compared with the wild type is much in excess of that expected (<1%) for highly conserved regions of the parvovirus genome [35]. All mutations were silent except that at nt 1466 (G
C), which had resulted in an amino acid change from serine to threonine at position 344 [2], immediately downstream of the Walker box A of the nucleoside triphosphate (NTP) binding site (amino acid positions 323343) [6]. As cytotoxicity is closely associated with functional NTP binding, it may be that this mutation facilitated persistence by modifying cytotoxicity [8]. It is also important to note that threonine at position 344 is typical of adeno-associated virus type 2 (AAV-2) [3], which infects skeletal muscle, disrupting the troponin T gene, TNNT1, and integrating into human chromosome 19 (19q13.3-qter) at the AAVS1 locus [7]. In addition, we have reported the detection of parvovirus B19 DNA in the skeletal muscle of a case of chronic fatigue syndrome (CFS) [2]; nucleotide sequencing of the same region revealed two mutations compared with the published sequence, both of which were silent: nt 1530, A
G and 1638, A
C (GenBank accession no. 324453).
Cases of myositis as well as increases in serum muscle enzymes [8] have been associated with acute B19 infection. These include a child with juvenile dermatomyositis [9], another with B19-associated interstitial lung disease, hepatitis and myositis [10], a case of probable systemic lupus erythematosus associated with increased creatine kinase and aldolase [8] and a series of four cases from which B19 DNA was detected in skeletal muscle [11]. The case reported by Chevrel and colleagues [1] was positive for HLA-DR4, which has been associated with the development of and increased duration of arthritis following B19 infection [12, 13]. HLA-DR3 and DR4 are over-represented in cases of polymyositis [14, 15].
Parvovirus B19 exhibits a variety of virulence mechanisms which have relevance to the genesis of rheumatic disease and myositis [16], may result in chronic dysregulation of cytokines with raised circulating tumour necrosis factor- (TNF-
) and interferon-
(IFN-
) [17], and may possibly integrate into peripheral blood leucocytes [18]. How it might achieve persistence and damage in skeletal muscle remains to be clarified.
Notes
Correspondence to: J. R. Kerr.
References