Neurovirulence of herpes simplex virus types 1 and 2 isolates in diseases of the central nervous system.
Herpes simplex virus (HSV) isolates derived from the central nervous system of ten patients with HSV-1-induced encephalitis, one patient with multiple sclerosis, and 14 patients with HSV-2-induced meningitis were investigated for neurovirulence by assaying the LD50 after nose and intracerebral (i.c.) inoculation of mice. HSV-1 encephalitis strains were significantly more virulent after nose inoculation (i.e. neuroinvasive) when compared with HSV-1 isolates from patients with oral lesions only, whereas HSV-2 meningitis strains were significantly more virulent after i.c. inoculation when compared with HSV-2 isolates from patients with genital lesions only. No correlation between high neurovirulence (defined as low LD50 for both routes of infection) and replication in cell cultures of neuronal and non-neuronal cell lines was found, but the weakly neurovirulent HSV-1 strain isolated from a patient with multiple sclerosis gave low replication yields. After nose inoculation, a highly neuroinvasive HSV-1 laboratory reference strain replicated to high titers in nose tissue, the trigeminal ganglia and brainstem, while a strain with low neuroinvasiveness but high i.c. virulence replicated less well in the brainstem. Neuroinvasiveness of the virus strain might be one factor of relevance in the pathogenesis of HSV-1 encephalitis in man.
Bergström
T
T
Department of Clinical Virology, University of Göteborg, Sweden.
Alestig
K
K
Svennerholm
B
B
Horal
P
P
Sköldenberg
B
B
Vahlne
A
A
D000818:Animals; D004660:Encephalitis / Q000209:etiology / Q000382:microbiology*; D006801:Humans; D007928:Lethal Dose 50; D008581:Meningitis / Q000209:etiology / Q000382:microbiology*; D051379:Mice; D009103:Multiple Sclerosis / Q000209:etiology / Q000382:microbiology*; D018139:Simplexvirus / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology; D013045:Species Specificity; D014774:Virulence; D014779:Virus Replication