Polymerase chain reaction detection and clinical significance of varicella-zoster virus in cerebrospinal fluid from human immunodeficiency virus-infected patients.

Varicella-zoster virus (VZV) causes ocular and other central nervous system (CNS) disease in human immunodeficiency virus (HIV)-infected persons. To study the prevalence of CNS disease due to VZV, cerebrospinal fluid (CSF) specimens from 84 consecutive HIV-infected patients with new neurologic symptoms were tested for VZV DNA by a polymerase chain reaction (PCR) assay. Six patients were PCR-positive for VZV in CSF; 3 additional patients were subsequently identified who were not part of the serial population sample. Among these 9 patients, all had clinical presentations consistent with ocular and other CNS disease due to VZV; 4 were without zoster on presentation. Sustained improvement in association with antiviral therapy was observed in 3. Therefore, VZV DNA was detected in the CSF of 7% of HIV-infected patients presenting with neurologic symptoms; the diagnosis of VZV-related CNS disease was facilitated by this assay; improvement in association with antiviral therapy was observed in some patients.

Neural spread of herpes simplex virus after anterior chamber inoculation.

A genetically engineered herpes simplex virus type 1 (HSV-1, strain RH116) that expresses beta-galactosidase (beta-gal) was used as a marker to trace the route of interocular spread of HSV-1 after anterior chamber (AC) inoculation into BALB/c mice. Because RH116 is thymidine kinase deficient (TK-), the wild-type TK+ KOS strain of HSV-1 was used as a helper virus to complement RH116 during in vivo infection. After coinfection of BALB/c mice with RH116 and KOS in the AC of one eye, beta-gal expression by RH116 was detected in both the eyes and in the central nervous system (CNS). Our results suggest that after AC inoculation into BALB/c mice: (1) virus spreads from the injected eye to the CNS through parasympathetic fibers of the oculomotor nerve that supply the iris and ciliary body; (2) virus spread in the CNS is limited primarily to nuclei of the visual system and the suprachiasmatic area of the hypothalamus; and (3) virus is transmitted from the CNS to the retina of the contralateral eye by retrograde axonal transport through the optic nerve along the endocrine-optic pathway between the retina and the suprachiasmatic nucleus of the hypothalamus.

A critical role for ACAID in the distinctive pattern of retinitis that follows anterior chamber inoculation of HSV-1.

To test the hypothesis that ACAID induction is instrumental in producing the distinctive pattern of retinal pathology that follows anterior chamber inoculation of HSV-1 in BALB/c mice, panels of mice received uniocular anterior chamber, uniocular intravitreal, and bilateral anterior chamber inoculations of HSV-1. It was found that contralateral retinitis developed after the first two routes, and ACAID was induced by all three. Enucleation of eyes inoculated with HSV-1 before 3 days post-inoculation (but not thereafter) prevented both ACAID and contralateral retinitis. Intracameral inoculations of HSV-2 induced vigorous delayed hypersensitivity and failed to incite contralateral retinitis. It is concluded that ACAID induction plays a crucial role in the pathogenesis of contralateral retinitis following anterior chamber inoculation of HSV-1.