Oligodendrocytes from human donors differ in resistance to herpes simplex virus 1 (HSV‐1)

Abstract

Primary cultures of human oligodendrocytes (HOLs) were established from six different donors. Differences in resistance to infection with herpes simplex virus 1 (HSV-1) were determined between the primary cultures of HOL in tissue culture infective dose 50 (TCID 50 ), indirect immunofluoresence (IF), and serial electron microscopy (EM) studies. Virus production at different multiplicities of infection (MOIs) indicated that differences in HSV-1 replication were statistically significant and MOIdependent. Overall, virus yield from the HOL cultures infected at an MOI of 1 increased up to 6 days postinfection (PI); no additional enhancement occurred at 7 days PI. However, differences in the replication capacity of the six HOL cultures observed at 5 days PI persisted at 6 and 7 days PI. When taken together, the results of these investigations indicate that, similar to experimental animals, resistance to HSV-1 differs between primary cultures of HOL and is donor-dependent. The results also raise the possibility that similar to experimental animals, resistance to HSV-1, mediated at the level of HOL, may be genetically determined. Furthermore, permissive infections of primary cultures of HOL were established with HSV-1 over a wide range of MOIs, similar to results obtained with viral infection of primary murine oligodendrocytes, but neither latent nor abortive infections of HOL were induced in vitro, even at very low MOIs. Resistance to HSV-1, mediated by glial cells, is a nonimmune mechanism that may influence the development of acute CNS infection in man as well as individual susceptibility to this virus. GLIA 38: 87-92, 2002.

The Role of Herpes Simplex Virus Type 1 Infection in Demyelination of the Central Nervous System

“…Moreover, in that study, demyelination was followed by remyelination, although it was incomplete and the presence of scars was observed. As in studies with experimental animals, resistance to HSV-1 varies between primary cultures of human OLs and is donor-dependent [ 115 ]. Susceptibility to HSV-1 encephalitis may be caused at least partly by mutations in Toll-like receptors that decrease the intrinsic resistance of CNS cells (neurons and OLs in particular) to HSV-1 infection [ 116 , 117 ].…”

“…For instance, when a recombinant HSV-1 constitutively expressing interleukin-2 (IL-2) was inoculated into mice, it provoked CNS demyelination and optic neuropathy, whereas infection with recombinant viruses expressing IL-4, gamma interferon, IL-12p35, IL-12p40, or IL-12p70 did not induce this effect [ 131 ]. On the other hand, donor-dependent differences in resistance to infection with HSV-1 were established in primary cultures of human OLs [ 115 ].…”

The glial growth factors deficiency and synaptic destabilization hypothesis of schizophrenia

“…Glial cells display genetically determined individual differences to virus infections [112] and are infected by a large number of viruses (for review [113,114]). Especially interesting in this regard is the human herpes virus-6 (HHV-6) and the JC virus (JCV).…”

Allelic association of sequence variants in the herpes virus entry mediator-B gene (PVRL2) with the severity of multiple sclerosis

“…44 Consistent with this observation and the results reported here, recent experimental studies have shown that human oligodendrocytelike cells are highly susceptible to HSV-1 infection, 45 and that differences in virus-host cell interactions, and hence HSV-1 susceptibility, are probably genetically determined. 46 Interestingly, another member of the Herpesviridae family, human herpesvirus 6 , has also been associated with MS. 47 In summary, our study suggests that sequence variants in a 16.6 kb block spanning intron 1 to intron 2 of PVRL2 may influence the severity of MS in a subset of patients. It is currently unknown whether these variants, or others in LD with them, alter the functionality of the viral receptor region, or affect gene splicing.…”