Inflammatory sensory polyradiculopathy and reactivated peripheral nervous system infection in a genital herpes model.
To study effects of herpesvirus reactivation on the nervous system, mice with latent genital herpes simplex virus type 2 (HSV-2) infections were immunosuppressed. Reactivated infection was detected by virus isolation or by antigen screening in histological sections of spines that contained cords, roots, and dorsal root ganglia. In ganglia, viral antigen was restricted to 2 distinct groups at T9-L2, and L6-S2 levels. In some ganglia, antigen was found in up to 4% of non-contiguous neurons, in their axons, and in endoneurial and satellite cells. Nerve roots distal to ganglia contained a few antigen-positive endoneurial cells and axons, but convincing antigen was not seen in proximal roots. Rare foci of anterior horn cells in the lower cord were the only central sites found to contain antigen. Comparison of antigen-containing ganglionic neuron counts to vaginal culture data indicate that peripheral virus shedding may depend on the number of neurons with reactivated infection. In non-immunosuppressed, latently infected mice, virus recovery was restricted to ganglionic explants from lower thoracic and lumbosacral regions; these ganglia contained no infectious virus in homogenates and no detectable antigen. These mice had an inflammatory polyradiculopathy in a similar distribution to virus found in latent and reactivated infection. The data show that genital HSV-2 infection can result in more extensive ganglionic latency and peripheral nervous system disease than has previously been recognized. Immunosuppression leads to reactivation and widespread, anatomically restricted antigen expression in many ganglia, consistent with the innervation of the genitourinary tract. Decalcified spine preparations provide a sensitive and simple way to detect virus reactivations and disease in these neural tissues.
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D005260:Female; D005727:Ganglia, Spinal / Q000473:pathology / Q000503:physiopathology; D006558:Herpes Genitalis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010525:Peripheral Nerves / Q000382:microbiology / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000382:microbiology* / Q000473:pathology; D011129:Polyradiculoneuropathy / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D018139:Simplexvirus / Q000254:growth & development* / Q000276:immunology / Q000302:isolation & purification; D014621:Vagina / Q000382:microbiology; D014775:Virus Activation
D000956:Antigens, Viral