NKT cell activation by local α-galactosylceramide administration decreases susceptibility to HSV-2 infection

Iversen, Marie B.; Jensen, Simon Kok; Hansen, Anne Louise; Winther, Henriette; Issazadeh‐Navikas, Shohreh; Reinert, Line S.; Holm, Christian K.

doi:10.1016/j.imbio.2014.12.019

Cited by 15 publications

(11 citation statements)

References 39 publications

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“…The model explicitly follows T-cells because the greatest amount of data exists to describe the expansion and clearance of these cells in genital mucosa. While we recognize that NK cell or antibody dependent complement mediated cytotoxicity may contribute in a meaningful way to clearance of infected cells,[ 30 , 31 ] there is inadequate available dynamic and functional mucosal immune data during HSV-2 clearance to partition the cytolytic immune response into these more detailed components. Similarly, we do not explicitly differentiate between CD4+ and CD8+ T-cells because it is unknown what proportion of HSV-2 clearance can be attributed to each subset of cells in humans.…”

Section: Resultsmentioning

confidence: 99%

Mathematical Modeling Predicts that Increased HSV-2 Shedding in HIV-1 Infected Persons Is Due to Poor Immunologic Control in Ganglia and Genital Mucosa

et al. 2016

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A signature feature of HIV infection is poor control of herpes virus infections, which reactivate from latency and cause opportunistic infections. While the general mechanism underlying this observation is deficient CD4+T-cell function, it is unknown whether increased severity of herpes virus infections is due primarily to poor immune control in latent or lytic sites of infection, or whether CD4+ immunodeficiency leads to more critical downstream deficits in humoral or cell-mediated immunologic responses. Here we compare genital shedding patterns of herpes simplex virus-2 (HSV-2) in 98 HIV infected and 98 HIV uninfected men matched on length of infection, HSV-1 serostatus and nationality. We demonstrate that high copy HSV-2 shedding is more frequent in HIV positive men, particularly in participants with CD4+ T-cell count <200/μL. Genital shedding is more frequent due to higher rate of shedding episodes, as well as a higher proportion of prolonged shedding episodes. Peak episode viral load was not found to differ between HIV infected and uninfected participants regardless of CD4+ T-cell count. We simulate a mathematical model which recapitulates these findings and identifies that rate of HSV-2 release from neural tissue increases, duration of mucosal cytolytic immune protection decreases, and cell-free viral lifespan increases in HIV infected participants. These results suggest that increased HSV-2 shedding in HIV infected persons may be caused by impaired immune function in both latent and lytic tissue compartments, with deficits in clearance of HSV-2 infected cells and extracellular virus.

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Section: Resultsmentioning

confidence: 99%

Mathematical Modeling Predicts that Increased HSV-2 Shedding in HIV-1 Infected Persons Is Due to Poor Immunologic Control in Ganglia and Genital Mucosa

et al. 2016

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“…This rationale underlies a plethora of studies investigating the use of α-GalCer as a vaccine adjuvant. So far, α-GalCer has been tested as an adjuvant for human papillomavirus (HPV) [ 203 ], IAV [ 204 , 205 , 206 , 207 , 208 , 209 , 210 , 211 , 212 , 213 ], HSV-2 [ 214 , 215 ], HIV-1 [ 216 , 217 ] and human metapneumovirus [ 218 ] vaccines.…”

Section: Viral Immune Evasion and Immune Modulationmentioning

confidence: 99%

Ceramide and Related Molecules in Viral Infections

Beckmann

Becker

2021

IJMS

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Ceramide is a lipid messenger at the heart of sphingolipid metabolism. In concert with its metabolizing enzymes, particularly sphingomyelinases, it has key roles in regulating the physical properties of biological membranes, including the formation of membrane microdomains. Thus, ceramide and its related molecules have been attributed significant roles in nearly all steps of the viral life cycle: they may serve directly as receptors or co-receptors for viral entry, form microdomains that cluster entry receptors and/or enable them to adopt the required conformation or regulate their cell surface expression. Sphingolipids can regulate all forms of viral uptake, often through sphingomyelinase activation, and mediate endosomal escape and intracellular trafficking. Ceramide can be key for the formation of viral replication sites. Sphingomyelinases often mediate the release of new virions from infected cells. Moreover, sphingolipids can contribute to viral-induced apoptosis and morbidity in viral diseases, as well as virus immune evasion. Alpha-galactosylceramide, in particular, also plays a significant role in immune modulation in response to viral infections. This review will discuss the roles of ceramide and its related molecules in the different steps of the viral life cycle. We will also discuss how novel strategies could exploit these for therapeutic benefit.

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“…Furthermore, cellular recycling of CD1d was also inhibited by the viral protein VP22 working along US3 (Liu J. et al, 2016). Importantly, the administration of α-galactosylceramide, an NKT ligand that elicits the recruitment of these cells to the vaginal tissue was reported to decrease the susceptibility of mice upon HSV-2 intravaginal infection (Iversen et al, 2015).…”

Section: Hsvs Down-modulate the Antiviral Activities Of The Complemenmentioning

confidence: 99%

Herpes Simplex Virus Evasion of Early Host Antiviral Responses

Tognarelli

Palomino

Corrales

et al. 2019

Front. Cell. Infect. Microbiol.

100

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Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) have co-evolved with humans for thousands of years and are present at a high prevalence in the population worldwide. HSV infections are responsible for several illnesses including skin and mucosal lesions, blindness and even life-threatening encephalitis in both, immunocompetent and immunocompromised individuals of all ages. Therefore, diseases caused by HSVs represent significant public health burdens. Similar to other herpesviruses, HSV-1 and HSV-2 produce lifelong infections in the host by establishing latency in neurons and sporadically reactivating from these cells, eliciting recurrences that are accompanied by viral shedding in both, symptomatic and asymptomatic individuals. The ability of HSVs to persist and recur in otherwise healthy individuals is likely given by the numerous virulence factors that these viruses have evolved to evade host antiviral responses. Here, we review and discuss molecular mechanisms used by HSVs to evade early innate antiviral responses, which are the first lines of defense against these viruses. A comprehensive understanding of how HSVs evade host early antiviral responses could contribute to the development of novel therapies and vaccines to counteract these viruses.

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NKT cell activation by local α-galactosylceramide administration decreases susceptibility to HSV-2 infection

Cited by 15 publications

References 39 publications

Mathematical Modeling Predicts that Increased HSV-2 Shedding in HIV-1 Infected Persons Is Due to Poor Immunologic Control in Ganglia and Genital Mucosa

Mathematical Modeling Predicts that Increased HSV-2 Shedding in HIV-1 Infected Persons Is Due to Poor Immunologic Control in Ganglia and Genital Mucosa

Ceramide and Related Molecules in Viral Infections

Herpes Simplex Virus Evasion of Early Host Antiviral Responses

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