Effect of Apolipoprotein E on the Cerebral Load of Latent Herpes Simplex Virus Type 1 DNA

Abstract

Herpes simplex virus type 1 (HSV-1) is neurotropic and enters a latent state lasting the lifetime of the host. This pathogen has recently been proposed as a risk factor for Alzheimer's disease (AD) in conjunction with apolipoprotein E4 (ApoE4). In a murine acute infection model, we showed that viral neuroinvasiveness depends directly on the overall ApoE dosage and especially on the presence of isoform ApoE4. If an interaction between ApoE and HSV-1 is involved in AD, it may occur during latency rather than during acute infection. Certainly, ApoE plays an important role in late-onset AD, i.e., at a time in life when the majority of people harbor HSV-1 in their nervous system. In the present work, wild-type, APOE knockout, APOE3, and APOE4 transgenic mice were used to analyze the influence of the ApoE profile on the levels of latent virus DNA. The knockout mice had significantly lower concentrations of the virus in the nervous system than the wild-type mice, while the APOE4 mice had very high levels in the brain compared to the APOE3 animals. ApoE4 seems to facilitate HSV-1 latency in the brain much more so than ApoE3. The APOE dosage correlated directly with the HSV-1 DNA concentration in the brain, strengthening the hypothesis that HSV-1, together with ApoE, might be involved in AD.

Effect of human apolipoprotein E genotype on the pathogenesis of experimental ocular HSV-1

“…In our ocular route of HSV-1 inoculation, we found similar results, i.e., both C57Bl/6 mice and apoE4 mice harbor significantly higher copy numbers of HSV-1 DNA compared with apoE3 mice. These results support our previous findings (Bhattacharjee et al, 2006) as well as those of others (Burgos et al, 2003;Burgos et al, 2006) that murine apoE is analogous to human apoE4 in terms of HSV-1 neuroinvasiveness.…”

“…In a hematogenous route of HSV-1 inoculation, mouse apoE was analogous to the human apoE4 (Burgos et al, 2003;Burgos et al, 2006). In our ocular route of HSV-1 inoculation, we found similar results, i.e., both C57Bl/6 mice and apoE4 mice harbor significantly higher copy numbers of HSV-1 DNA compared with apoE3 mice.…”

Herpes simplex infection and the risk of Alzheimer's disease: A nested case-control study

“…A possible connection is further supported by studies demonstrating the detection of HSV1 within brain tissue from patients with AD and specifically within amyloid plaques [6][7][8][9][10], and by the finding that HSV1 infection can induce amyloid beta production and tau hyperphosphorylation in cultured neural cell types [11][12][13][14][15][16][17]. An effect of APOE genotype for HSV1 spread has also been reported [8,[18][19][20][21][22].…”

Apolipoprotein 4 may increase viral load and seizure frequency in mesial temporal lobe epilepsy patients with positive human herpes virus 6B

“…Previous studies indicate that ApoE4 facilitates the infection of herpes simplex virus (HSV)-1 in CNS, and its dosage is directly correlated with HSV-1 DNA concentration [19,20]. However, little is known about the association between ApoE4 and HHV-6B in MTLE.…”