Human herpesvirus-6 entry into the central nervous system through the olfactory pathway

Abstract

Viruses have been implicated in the development of neurodegenerative diseases, such as Alzheimer's, Parkinson’s, and multiple sclerosis. Human herpesvirus-6 (HHV-6) is a neurotropic virus that has been associated with a wide variety of neurologic disorders, including encephalitis, mesial temporal lobe epilepsy, and multiple sclerosis. Currently, the route of HHV-6 entry into the CNS is unknown. Using autopsy specimens, we found that the frequency of HHV-6 DNA in the olfactory bulb/tract region was among the highest in the brain regions examined. Given this finding, we investigated whether HHV-6 may infect the CNS via the olfactory pathway. HHV-6 DNA was detected in a total of 52 of 126 (41.3%) nasal mucous samples, showing the nasal cavity is a reservoir for HHV-6. Furthermore, specialized olfactory-ensheathing glial cells located in the nasal cavity were demonstrated to support HHV-6 replication in vitro. Collectively, these results support HHV-6 utilization of the olfactory pathway as a route of entry into the CNS.

Long-Distance Interferon Signaling within the Brain Blocks Virus Spread

“…A large number of viruses are capable of entering the brain through the olfactory mucosa. These viruses include rabies, Sindbis, pseudorabies, Borna, influenza, polio, herpes, and others (2)(3)(4)(5)(6)(7)(8)(9). The brain is particularly susceptible to cytolytic agents, as the relative lack of neuronal replacement in most regions of the central nervous system (CNS) exacerbates the longterm ramifications of cytopathic viral infection.…”

Beneficial response of cervical dystonia spasmodic torticollis to cidofovir, an acyclic phosphonate analog (s-1-3-hydroxy-2- phosphonylmethoxypropyl) of cytosine

“…[11][12][13][14][15] HHV6 enters the central nervous system through the olfactory pathway and replicates in neural cells, but the primary targets of HHV6 replication are CD4+ and T-cells, B-cells, monocytes, macrophages, and epithelial cells. [4][5][6][7] This case report is not a proof of cause, but the repeated consistent falls in HHV6 serum antibody titer and the apparent clinical response to cidofovir are striking ( Cidofovir is an acyclic phosphonate nucleotide analog of deoxycytidine monophosphate.…”

“…1,2 Other potentially nephrotoxic agents, ie, aminoglycosides or nonsteroidal anti-inflammatory agents, should be avoided during treatment with cidofovir. 8,[11][12][13][14] Cidofovir and probenecid share small sulfur moieties and may cause sulfur toxicity. Preliminary testing with initial small doses of cidofovir are indicated if sulfonamide sensitivity is suspected.…”

Viruses in human central nervous system — invasion, transmission, and latency: a literature review

“…Вновь продуцированные вирионы HSV1 мигрируют в струк-туры лимбической системы -гипоталамус, гиппокамп и миндалину [1,3], поэтому при HSV энцефалите наибольшие повреждения выявляют в лимбической системе [4]. Обонятельный тракт также являет путем проникновения в ЦНС герпеса 6 типа (HHV6) [5,6]. По данным патологоанатомического исследования, в 41% наблюдений в обонятельной луковице обнаружен HHV6 [5,6]; у 18% больных при мезиальной височной эпилепсии (MTLE синдром) в гиппокампе обнаружены вирусы HSV1, HHV6 и HHV8.…”

“…Обонятельный тракт также являет путем проникновения в ЦНС герпеса 6 типа (HHV6) [5,6]. По данным патологоанатомического исследования, в 41% наблюдений в обонятельной луковице обнаружен HHV6 [5,6]; у 18% больных при мезиальной височной эпилепсии (MTLE синдром) в гиппокампе обнаружены вирусы HSV1, HHV6 и HHV8.…”