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

Han, Xiao; Lundberg, Patric; Tanamachi, Becky; Openshaw, Harry; Longmate, Jeffrey; Cantin, Edouard M.

doi:10.1128/jvi.75.6.3048-3052.2001

Cited by 86 publications

(81 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…71 Male IFNg or IFNg receptor knockout mice infected with herpes simplex virus type-1 have a higher frequency of reactivation and a higher associated mortality than wild-type mice, whereas there is no difference between knockout and wild-type females. 72 Taken together with previous studies, our study provides further evidence that there is an association between IFNG polymorphisms and susceptibility to sporadic MS. Genetic variation in IFNg may in part account for gender differences in susceptibility to MS.…”

Section: Discussionsupporting

confidence: 86%

IFNG polymorphisms are associated with gender differences in susceptibility to multiple sclerosis

et al. 2005

View full text Add to dashboard Cite

Interferon-gamma (IFNg) treatment is deleterious in multiple sclerosis (MS). MS occurs twice as frequently in women as in men. IFNg expression varies by gender. We studied a population-based sample of US MS patients and ethnicity-matched controls and independent Northern Irish and Belgian hospital-based patients and controls for association with MS, stratified by gender, of an intron 1 microsatellite [I1 (761)

show abstract

Section: Discussionsupporting

confidence: 86%

IFNG polymorphisms are associated with gender differences in susceptibility to multiple sclerosis

et al. 2005

View full text Add to dashboard Cite

show abstract

“…1E). Furthermore, the higher relative resistance of adult female mice to HSV-1 infection is noted in the literature (33)(34)(35) and is consistently supported in our empirical studies (unpublished observations). Our data provide compelling evidence that the sex bias in susceptibility could be mechanistically linked to a disparity in antiviral gene induction during acute infection.…”

supporting

confidence: 77%

Impact of Type I Interferon on the Safety and Immunogenicity of an Experimental Live-Attenuated Herpes Simplex Virus 1 Vaccine in Mice

Royer

Carr

Chucair-Elliott

et al. 2017

J Virol

View full text Add to dashboard Cite

Viral fitness dictates virulence and capacity to evade host immune defenses. Understanding the biological underpinnings of such features is essential for rational vaccine development. We have previously shown that the live-attenuated herpes simplex virus 1 (HSV-1) mutant lacking the nuclear localization signal (NLS) on the ICP0 gene (0ΔNLS) is sensitive to inhibition by interferon beta (IFN-␤) in vitro and functions as a highly efficacious experimental vaccine. Here, we characterize the host immune response and in vivo pathogenesis of HSV-1 0ΔNLS relative to its fully virulent parental strain in C57BL/6 mice. Additionally, we explore the role of type 1 interferon (IFN-␣/␤) signaling on virulence and immunogenicity of HSV-1 0ΔNLS and uncover a probable sex bias in the induction of IFN-␣/␤ in the cornea during HSV-1 infection. Our data show that HSV-1 0ΔNLS lacks neurovirulence even in highly immunocompromised mice lacking the IFN-␣/␤ receptor. These studies support the translational viability of the HSV-1 0ΔNLS vaccine strain by demonstrating that, while it is comparable to a virulent parental strain in terms of immunogenicity, HSV-1 0ΔNLS does not induce significant tissue pathology.IMPORTANCE HSV-1 is a common human pathogen associated with a variety of clinical presentations ranging in severity from periodic "cold sores" to lethal encephalitis. Despite the consistent failures of HSV subunit vaccines in clinical trials spanning the past 28 years, opposition to live-attenuated HSV vaccines predicated on unfounded safety concerns currently limits their widespread acceptance. Here, we demonstrate that a live-attenuated HSV-1 vaccine has great translational potential.KEYWORDS HSV-1, T cells, antibody, cornea, mouse, neovascularization S trategies for vaccine development have transitioned largely from empirical to so-called "next-generation" or rational approaches during the past 2 decades, a shift largely driven by technological advances and a better understanding of how innate immunity influences the generation of adaptive protection (1, 2). Despite these breakthroughs, the average person still acquires multiple herpesvirus infections during childhood (3). A licensed vaccine, however, exists only for varicella-zoster virus (VZV) (4). The live-attenuated Oka vaccine for VZV is generally well tolerated and has significantly reduced the incidence of VZV infection, morbidity, and mortality in the United States (5, 6). Furthermore, epidemiologic studies indicate that acquisition of herpes simplex virus 1 (HSV-1) has shifted toward early to late adolescence in recent decades within the United States, potentially creating an opportunity to introduce an effective prophylactic HSV-1 vaccine into the childhood vaccine regimen (7). HSV vaccines have been tested in multiple clinical trials, but these studies have focused on protein subunit vaccines

show abstract

“…These discrepancies may be due to different animal strains, different virus strains or different animal models. We have shown that the effect of LAT on the HSV-1 latency-reactivation phenotype is mouse strain dependent , whereas others have reported a gender bias (Han et al, 2001). …”

Section: Discussionmentioning

confidence: 99%

The bovine herpesvirus-1 LR ORF2 is critical for this gene's ability to restore the high wild-type reactivation phenotype to a herpes simplex virus-1 LAT null mutant

Mott

Osório

Jin

et al. 2003

Journal of General Virology

View full text Add to dashboard Cite

The bovine herpesvirus-1 LR ORF2 is critical for this gene's ability to restore the high wild-type reactivation phenotype to a herpes simplex virus-1 LAT null mutant During neuronal latency of herpes simplex virus (HSV)-1, the latency-associated transcript (LAT) is the only viral gene readily detectable. LAT is required for the high-level reactivation phenotype in animal models. LAT's anti-apoptotic activity was recently demonstrated by our group and it was proposed that LAT's anti-apoptotic function is involved in enhancing the reactivation phenotype. Recently, using chimeric virus CJLAT, it was shown that the reactivation phenotype of LAT " mutant dLAT2903 can be restored to wild-type levels by inserting the bovine herpes virus (BHV)-1 latency-related (LR) gene into the LAT locus of this HSV-1 LAT deletion mutant. Although transcription of the LR gene, like LAT, inhibits apoptosis, LR appears to be multifunctional. To investigate whether the LR gene's anti-apoptotic function was responsible for restoring the high-reactivation phenotype, a mutated BHV-1 LR gene was inserted into the LAT locus of HSV-1 generating the chimeric virus CJLATmut. This mutation consists of three stop codons inserted just after the ATG of the first LR open reading frame (ORF2). In plasmids and in a BHV-1 mutant, this mutation eliminated the LR gene's anti-apoptotic activity, strongly suggesting that ORF2 encodes a protein responsible for LR's anti-apoptotic activity. Reactivation of the CJLATmut virus, in both rabbits and mice, was significantly lower than in wild-type McKrae virus (P=0?0001 and P=0?0003, respectively) and CJLAT virus, containing wild-type LR in place of LAT (P<0?0001) and was similar to LAT " dLAT2903 (P=0?8 and P=0?7, respectively). Thus, disruption of BHV-1 LR ORF2 eliminated the high-reactivation phenotype. INTRODUCTIONOver 80 % of adults in the United States harbour latent herpes simplex virus type 1 (HSV-1). Following primary peripheral infection of the eye, HSV-1 travels along axons via antegrade transport to sensory neurons of the trigeminal ganglia (TG) where latency is established. The latent virus reactivates sporadically as a result of stress, UV exposure and other unknown stimuli. Reactivations can also occur in the absence of known stimuli, which we have operationally defined as spontaneous reactivation. Following reactivation, HSV-1 travels along axons in a retrograde direction to the initial infection site, where it can replicate and cause recurrent disease (Andreansky et al., 1998;Roizman & Whitley, 2001). Recurrent HSV-1 infection in the eye can cause corneal scarring leading to the loss of vision. As a result, HSV-1 is one of the leading infectious causes of corneal blindness in the developed world (Liesegang et al., 1989). The mechanism(s) by which the latent virus reactivates and causes disease are currently not completely understood.The only gene that is actively transcribed during HSV-1 neuronal latency is the latency-associated transcript (LAT) (Rock et al., 1987b; Stevens et al., 1987). A stab...

show abstract

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

Cited by 86 publications

References 38 publications

IFNG polymorphisms are associated with gender differences in susceptibility to multiple sclerosis

IFNG polymorphisms are associated with gender differences in susceptibility to multiple sclerosis

Impact of Type I Interferon on the Safety and Immunogenicity of an Experimental Live-Attenuated Herpes Simplex Virus 1 Vaccine in Mice

The bovine herpesvirus-1 LR ORF2 is critical for this gene's ability to restore the high wild-type reactivation phenotype to a herpes simplex virus-1 LAT null mutant

Contact Info

Product

Resources

About