Detection of herpes simplex virus type 1 in rheumatic valvular tissue.
BACKGROUND
Rheumatic heart disease (RHD) is the most important sequela of rheumatic fever (RF): evidence that streptococcal infection is aetiological is prominent, but sometimes contradictory. Acute HSV-1 infection in mouse leads to carditis and valvulitis whereas recurrent infection results in inflammatory granulomatous lesions that resemble Aschoff bodies. Cells containing HSV-1 inclusions or virus infected giant cells appear similar to Anitschkow cells or Aschoff cells respectively. We hypothesized that HSV-1 infection also may be involved in RHD.


METHODS
Formalin-fixed, paraffin-embedded valvular tissue samples from 32 patients with RHD were investigated for evidence of HSV-1 infection. HSV-1 antigen was detected by immunohistochemistry, using HSV-1-specific monoclonal and polyclonal antibodies. HSV-1 glycoprotein D gene sequences were amplified by nPCR, using beta-globin gene amplification in the same samples as internal control. Valvular tissue from 5 cases of sudden death and 3 cases died of neisseria meningitis without a history of valvular disease was used for comparison. HSV-1-infected lung tissue was used as positive control.


RESULTS
HSV-1 antigens were detected in valvular tissues from 21 of 32 (65.6%) patients. Fifteen of these 21 (46.9% of cases), but no antigen-negative sample, were positive also for HSV DNA. Nucleotide sequence of PCR products was homologous to the targeted region of the HSV-1 glycoprotein D gene. HSV-1 antigen was present also in one case of sudden death but viral DNA was not found in any tissue sample from the comparison group. Results from reagent and positive controls were as anticipated.


CONCLUSIONS
This is the first study to show the presence of HSV-1 antigen and genomic DNA in valvular tissues from patients with RHD and provides evidence for an association of HSV-1 infection with some cases of rheumatic valvular disease.
Pan
Zhi-gang
ZG
Division of General Practice, Zhongshan Hospital, and Department of General Practice, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Wang
Xiu-nan
XN
Li
Yan-wen
YW
Zhang
Hong-yi
HY
Archard
Leonard C
LC
D000293:Adolescent; D000328:Adult; D000956:Antigens, Viral / Q000302:isolation & purification; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D006349:Heart Valve Diseases / Q000209:etiology / Q000821:virology; D006351:Heart Valves / Q000473:pathology / Q000821:virology*; D006561:Herpes Simplex / Q000473:pathology / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012214:Rheumatic Heart Disease / Q000473:pathology / Q000821:virology*; D014759:Viral Envelope Proteins / Q000235:genetics
D000956:Antigens, Viral; D004279:DNA, Viral; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1