The Influence of Androgens on Paralysis in Mice Following Intravenous Inoculation of Herpes Simplex Virus

Yirrell, David; Blyth, W. A.; Hill, Terry

doi:10.1099/0022-1317-68-9-2461

Cited by 18 publications

(15 citation statements)

References 9 publications

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“…This finding agrees with studies showingthat HSV-1-specific antibodies are generally more abundant in female mice than in male mice-a difference that disappears upon castration (22). Some authors have also reported HSV-1-infected males to have less severe clinical disease (17,39). Yirrell et al (39) showed that male mice were less susceptible to paralysis than female mice and that castration prior to infection increased the probability of disease in males to that in females; treatment with testosterone reversed this change.…”

Section: Discussionmentioning

confidence: 98%

“…Some authors have also reported HSV-1-infected males to have less severe clinical disease (17,39). Yirrell et al (39) showed that male mice were less susceptible to paralysis than female mice and that castration prior to infection increased the probability of disease in males to that in females; treatment with testosterone reversed this change. On the contrary, Han et al (14) showed that after infection with HSV-1 by corneal scarification, mortality and reactivation were more common in males.…”

Section: Discussionmentioning

confidence: 98%

“…Despite early reports of differences between the sexes with respect to herpes simplex virus type 1 (HSV-1) antibody titers in mice (22), in the severity of paralysis in mice after HSV-1 inoculation (17,39), and in the outcome of HSV-1 infection by corneal scarification (14), neither sex-dependent differences in infections with this pathogen nor associated diseases have been well studied. In addition, the literature contains little information on sex-dependent differences with respect to the outcome of hematogenous infection with HSV-1.…”

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confidence: 99%

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Herpes Simplex Virus Type 1 Infection via the Bloodstream with Apolipoprotein E Dependence in the Gonads Is Influenced by Gender

Ramı́rez

Sastre

Alfaro

et al. 2005

J Virol

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Herpes simplex virus type 1 (HSV-1) causes disease in humans and animals. Infection usually occurs via the neural route and possibly occurs via the hematogenous route. The latter, however, is the main route by which immunosuppressed individuals and neonates are infected. Gender-dependent differences in the incidence and severity of some viral infections have been reported. To detect differences between the sexes with respect to HSV-1 colonization and disease, the characteristics of both acute and latent infections in hematogenously infected male and female mice were compared. In acute infection, the female mice had a poorer outcome: HSV-1 colonization was more effective, especially in the gonads and brain. In the encephalon, the midbrain had the highest viral load. In latent infection, brain viral loads were not significantly different with respect to sex. Significant differences were seen, however, in the blood and trigeminal ganglia: HSV-1 seroprevalence was observed in females, with no virus detected in males. In brain dissections, only the cerebral cortex of the females had viral loads statistically higher than those observed in the males. The spread of the virus to several organs of interest during acute infection was examined immunohistochemically. Female mice showed greater viral immunostaining, especially in the adrenal cortex, gonads, and midbrain. In male mice, HSV-1 was detected predominantly in the adrenal cortex. It was also found that apolipoprotein E promotes virus colonization of the ovaries, the APOE gene dose being directly related to viral invasiveness.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

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Herpes Simplex Virus Type 1 Infection via the Bloodstream with Apolipoprotein E Dependence in the Gonads Is Influenced by Gender

Ramı́rez

Sastre

Alfaro

et al. 2005

J Virol

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“…Females are also disproportionately afflicted by autoimmune disease, such as lupus erythematosus, rheumatoid arthritis, myasthenia gravis, scleroderma, Sjögren's syndrome, multiple sclerosis, experimental allergic encephalomyelitis (EAE) (10,28,36), and herpes simplex virus (HSV). Despite early reports of differences in antibody titer (22) and severity of paralysis after HSV-1 inoculation of mice (18,38), gender-based differences in HSV-1 infection or in HSV-1-associated diseases have not been well studied.…”

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confidence: 99%

Gender Influences Herpes Simplex Virus Type 1 Infection in Normal and Gamma Interferon-Mutant Mice

Han¹,

Lundberg²,

Tanamachi³

et al. 2001

J Virol

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Gender influences the incidence and severity of some bacterial and viral infections and autoimmune diseases in animal models and humans. To determine a gender-based difference, comparisons were made between male and female mice inoculated with herpes simplex virus type 1 (HSV-1) by the corneal route. Mortality was higher in the male mice of the three strains tested: 129/Sv//Ev wild type, gamma interferon (IFN-␥) knockout (GKO), and IFN-␥ receptor knockout (RGKO). Similarly, in vivo HSV-1 reactivation occurred more commonly in male mice, but the male-female difference in reactivation was restricted to the two knockout strains and was not seen in the 129/Sv//Ev control. Comparison among male mice of the three strains showed a higher mortality of the RGKO mice and a higher reactivation rate of the GKO and RGKO mice than of the 129/Sv//Ev males. In contrast, female RGKO and GKO mice did not differ from female 129/Sv//Ev controls in either mortality or reactivation. HSV-1 periocular and eyelid disease was also more severe in male and dihydrotestosterone (DHT)-treated female mice than in control female mice. These results show a consistent gender difference in HSV-1 infection, with a worse outcome in male mice. In addition, the results comparing GKO and RGKO mice to controls show differences only in male mice, suggesting that some effects of IFN-␥, a key immunoregulatory molecule, are gender specific.

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“…This suggests that androgen receptors can overcome whatever mechanisms or regulations the apoE imposes on the transgenic mouse harboring the human ε 4 allele. Yirrell et al (1987) reported that androgens offered protection against systemic HSV-1 infection in mice. 4) Endosomal trafficking (endocytosis) and lipid rafts have been suggested by us (Hill et al, 2004) as playing a role in anterograde and retrograde transport of HSV.…”

Section: Apoe Isoform-dependent Effects and Hormones (Estrogens And Amentioning

confidence: 99%

Apolipoprotein E alleles can contribute to the pathogenesis of numerous clinical conditions including HSV-1 corneal disease

Hill

Bhattacharjee

Neumann

2007

Experimental Eye Research

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Apolipoprotein E (ApoE) alleles have been reported to affect the clinical outcome of numerous cardiovascular, neurodegenerative, and viral infectious diseases, including atherosclerosis, Alzheimer's disease (AD), hepatitis C, and HIV. The major alleles of ApoE are ε 2, ε 3, and ε 4. ApoE genotypes have been hypothesized to regulate many biological functions, resulting in significant changes in the onset and/or outcome (severity and duration) of several clinical conditions. Based on genetic analyses in human and animal studies using knockout (ApoE −/−) mice and mice transgenic for human ε 3 and ε 4, we present evidence that strongly suggests that the ApoE alleles can regulate the pathogenesis of ocular herpes simplex virus type 1 (HSV-1) infections. This review will summarize the major studies that support this hypothesis. Significant gender based differences in HSV-1 pathogenesis have also been reported, suggesting that hormonal regulation combined with ApoE genotype plays a significant role in HSV-1 pathogenesis. Identification of specific mechanisms in ocular HSV-1 infections related to the ApoE alleles and gender could lead to therapeutic intervention based on the properties of the apoE isoforms. While many clinical investigations have been reported and, to a lesser extent, transgenic mouse studies have been conducted, no specific mechanisms of how ApoE induces or alters clinical disease are known.

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The Influence of Androgens on Paralysis in Mice Following Intravenous Inoculation of Herpes Simplex Virus

Cited by 18 publications

References 9 publications

Herpes Simplex Virus Type 1 Infection via the Bloodstream with Apolipoprotein E Dependence in the Gonads Is Influenced by Gender

Herpes Simplex Virus Type 1 Infection via the Bloodstream with Apolipoprotein E Dependence in the Gonads Is Influenced by Gender

Gender Influences Herpes Simplex Virus Type 1 Infection in Normal and Gamma Interferon-Mutant Mice

Apolipoprotein E alleles can contribute to the pathogenesis of numerous clinical conditions including HSV-1 corneal disease

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