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Apolipoprotein E modulates establishment of HSV-1 latency and survival in a mouse ocular model
Partha S Bhattacharjee1, Donna M Neumann, David Stark
1Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
Purpose:
To evaluate and compare the neuroinvasiveness and neurovirulence after ocular HSV-1 infection in ApoE knockout (ApoE-/-) and control C57BL/6 (ApoE+/+) mice.
Methods:
Age-matched (14 weeks of age) C57BL/6J (ApoE+/+) female mice and female ApoE knockout (ApoE-/-) mice were inoculated by corneal scarification with HSV-1 strain 17Syn+. Analysis of HSV-1 replication in the mouse cornea was assessed through infectious virus assays of ocular (tear film) swabs at 1 to 5 days postinoculation (PI), slit-lamp examination (SLE) of corneas at PI days 1 to 7, and survival of infected mice. The contribution of apoE to the efficient establishment of latency was measured by real-time PCR quantitation of the latent viral genome in the trigeminal ganglia (TG) of infected mice.
Results:
These studies showed that HSV-1 strain 17Syn+ replicates efficiently in the eyes, regardless of the host ApoE genotype. Neither the scoring of corneal pathology via SLE nor the infectious virus assay of the tear film resulted in any statistical differences between ApoE knockout (-/-) mice or the C57BL/6 (ApoE+/+) mice. In mice latently infected with HSV-1, our real-time PCR data showed significantly lower viral copy numbers of HSV-1 DNA in ApoE knockout (ApoE-/-) mice compared with C57BL/6 (ApoE+/+) mice. C57BL/6 (ApoE+/+) mice are more susceptible to the neurovirulence of HSV-1 strain 17Syn+ than female ApoE knockout (-/-) mice, as demonstrated by the fact that 50% (7/14) of the female C57BL/6 (ApoE+/+) mice inoculated with 17Syn+ died, as opposed to none (0/14) of the age- and sex-matched ApoE knockout mice.
Conclusions:
These data indicate that age (14 weeks) and sex-matched (female) wild mice with an ApoE null background (ApoE-/-) are more resistant and less efficient in the establishment of latency compared with ApoE+/+ mice in the C57BL/6 background.
Insights
Apolipoprotein E (ApoE) knockout mice show increased resistance to herpes simplex virus type 1 (HSV-1) neurovirulence and reduced latency establishment compared to wild-type mice. These findings highlight ApoE
Area of Science:
- Neurovirology
- Immunology
- Genetics
Background:
- Herpes simplex virus type 1 (HSV-1) ocular infections can lead to neuroinvasion and neurovirulence.
- Apolipoprotein E (ApoE) plays a role in lipid transport and has been implicated in various neurological conditions.
- The role of ApoE in the host response to ocular HSV-1 infection and subsequent neuroinvasion is not fully understood.
Purpose of the Study:
- To compare neuroinvasiveness and neurovirulence of ocular HSV-1 infection in ApoE knockout (ApoE-/-) and control C57BL/6 (ApoE+/+) mice.
- To evaluate the impact of ApoE on the establishment of HSV-1 latency in the trigeminal ganglia.
Main Methods:
- Age- and sex-matched female C57BL/6J (ApoE+/+) and ApoE-/- mice were inoculated with HSV-1 strain 17Syn+ via corneal scarification.
- Viral replication was assessed by infectious virus assays and corneal pathology via slit-lamp examination.
- Neurovirulence was determined by mouse survival rates, and latency was quantified by real-time PCR of viral DNA in trigeminal ganglia.
Main Results:
- HSV-1 replicated efficiently in the eyes of both ApoE-/- and ApoE+/+ mice, with no significant differences in corneal pathology or viral shedding.
- ApoE-/- mice exhibited significantly lower viral copy numbers of latent HSV-1 DNA in the trigeminal ganglia compared to ApoE+/+ mice.
- C57BL/6 (ApoE+/+) mice showed increased susceptibility to neurovirulence, with a 50% mortality rate, whereas no ApoE-/- mice died.
Conclusions:
- ApoE deficiency in mice (ApoE-/-) confers resistance to HSV-1 neurovirulence following ocular infection.
- ApoE null background leads to less efficient establishment of HSV-1 latency in the trigeminal ganglia.
- These findings suggest ApoE plays a critical role in HSV-1 neuroinvasion and latency.
