Nectin-1 is an entry mediator for VZV infection of human neurons

2021 ◽  
Author(s):  
Labchan Rajbhandari ◽  
Priya Shukla ◽  
Balaji Jagdish ◽  
Abby Mandalla ◽  
Qingxue Li ◽  
...  
Keyword(s):  
Varicella Zoster Virus ◽  
Mammalian Cells ◽  
Primary Infection ◽  
Transcriptional Profiling ◽  
Varicella Vaccine ◽  
Ectopic Expression ◽  
Neuronal Model ◽  
Morbidity And Mortality ◽  
Varicella Zoster ◽  
Human Neurons

Varicella zoster virus (VZV) maintains lifelong latency in neurons following initial infection and can subsequently be reactivated to result in herpes zoster or severe neurological manifestations such as encephalitis. Mechanisms of VZV neuropathogenesis have been challenging to study due to the strict human tropism of the virus. While neuronal entry mediators of other herpesviruses, including herpes simplex virus, have been identified, little is known regarding how VZV enters neurons. Here, we utilize a human stem cell based neuronal model to characterize cellular factors that mediate entry. Through transcriptional profiling of infected cells, we identify the cell adhesion molecule nectin-1 as a candidate mediator of VZV entry. Nectin-1 is highly expressed in the cell bodies and axons of neurons. Either knockdown of endogenous nectin-1 or incubation with soluble forms of nectin-1 produced in mammalian cells results in a marked decrease in infectivity of neurons. Notably, while addition of soluble nectin-1 during viral infection inhibits infectivity, addition after infection has no effect on infectivity. Ectopic expression of human nectin-1 in a cell line resistant to productive VZV infection confers susceptibility to infection. In summary, we have identified nectin-1 as a neuronal entry mediator of VZV. IMPORTANCE Varicella zoster virus (VZV) causes chickenpox, gains access to neurons during primary infection where it resides lifelong, and can later be reactivated. Reactivation is associated with shingles and postherpetic neuralgia, as well as with severe neurologic complications including vasculitis and encephalitis. Although the varicella vaccine substantially decreases morbidity and mortality associated with primary infection, the vaccine cannot prevent development of neuronal latency and vaccinated populations are still at risk for reactivation. Furthermore, immunocompromised individuals are at higher risk for VZV reactivation and associated complications. Little is known regarding how VZV enters neurons. Here, we identify nectin-1 as an entry mediator of VZV in human neurons. Identification of nectin-1 as a neuronal VZV entry mediator could lead to improved treatments and preventative measures to reduce VZV related morbidity and mortality.

Varicella Vaccine Reflux

PEDIATRICS ◽  
1992 ◽  
Vol 89 (2) ◽  
pp. 354-354
Author(s):  
C. J. WHITE
Keyword(s):  
Varicella Zoster Virus ◽  
Primary Infection ◽  
Lymphoblastic Leukemia ◽  
Varicella Vaccine ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Varicella Zoster ◽  
Attenuated Virus ◽  
Sensory Root

In Reply.— Herpes zoster (shingles) is the dermatomal skin eruption resulting from the reactivation of varicella-zoster virus remaining latent in posterior sensory root ganglia following childhood chickenpox (the primary infection with varicella-zoster virus). Since the live attenuated varicella-zoster virus contained in the vaccine replicates in the vaccinee similar to the wild-type virus, establishment of latency is possible for the attenuated strain. Several publications have addressed latency of the attenuated virus following immunization. Two studies have examined the incidence of zoster in children with acute lymphoblastic leukemia (ALL) following immunization with live attenuated varicella-zoster virus.

Varicella-Zoster Virus (Varicella and Shingles)

2021 ◽  
Author(s):  
Anne Gershon
Keyword(s):  
Varicella Zoster Virus ◽  
Varicella Vaccine ◽  
The United States ◽  
Primary Immune Response ◽  
Wild Type Virus ◽  
High Dose ◽  
Healthy Children ◽  
Zoster Vaccine ◽  
Live Attenuated Vaccine ◽  
Varicella Zoster

A live attenuated vaccine against varicella (later also used to prevent zoster) was developed in 1974 by Takahashi and colleagues. Varicella vaccine was licensed for universal immunization of healthy children in the United States in 1995. It is also now used for this purpose in at least 15 additional countries all over the world. Varicella is disappearing in the US. Varicella vaccine has proven extremely safe and side effects are unusual, mild, and less serious than varicella or its complications. 85% of children are protected completely after 1 dose; the 15% who develop varicella despite immunization usually (but not always) have mild infections. These 15%, however, can transmit the wild type virus to others. Therefore, for optimal effect, 2 doses are required, mostly to address children who did not have an optimal primary immune response after the first dose. Waning immunity does not seem to pose a serious problem, but surveillance of vaccinees is continuing. It was demonstrated in 2005 that at a high dose of vaccine – 15 times higher than that used for prevention of varicella in children - zoster in adults can also be safely prevented. The live attenuated zoster vaccine is effective in approximately 50% of healthy individuals over age 60 who have had varicella in the past, and therefore have latent infection with varicella-zoster virus. It is given as one dose, but its effect runs out about 8 years after vaccination. In 2017, a new vaccine against zoster was also introduced. This is a subunit vaccine which does not contain contagious virus. It is even more effective than the older zoster vaccine and is over 95% effective in adults 50–≥70 years of age in preventing zoster and post herpetic neuralgia.

scholarly journals Kestabilan Model Matematika Infeksi Primer Penyakit Varicella Dan Infeksi Rekuren Penyakit Herpes Zoster Oleh Virus Varicella Zoster

2020 ◽  
Vol 17 (1) ◽  
pp. 82-91
Author(s):  
Hardiyanti ◽  
R Ratianingsih ◽  
Hajar
Keyword(s):  
Herpes Zoster ◽  
Stability Analysis ◽  
Varicella Zoster Virus ◽  
Critical Point ◽  
Postherpetic Neuralgia ◽  
Primary Infection ◽  
Skin Diseases ◽  
Varicella Zoster ◽  
Stable Conditions ◽  
Disease Free

Varicella and herpes zoster are two infectious skin diseases of human that caused by varicella zoster virus, where varicella disease is a primary infection that often infected younger people while herpes zoster disease is a recurrent disease that often infected older people because of reactivation of latent varicella-zoster virus. If the pain caused by herpes zoster after recurrent phase is a appeared then the condition is known as postherpetic neuralgia. This study builds a mathematical model of primary infection (varicella disease) and recurrent infection (herpes zoster disease) developed from the SIR model (Susceptible, Infected, Recovered). The human population is divided into seven subpopulations, namely susceptible, infection, recovered of varicella, herpes zoster and postherpetic neuralgia subpopulation. Stability analysis at the critical point by linearization method gives a critical point 𝑇1 that guaranted to exist and unstable if 𝛼 𝜇(𝛽1+𝜇) 𝐴 , while the critical point 𝑇1 does not have any reqruitment. Stability analysis at the endemic disease-free critical point is represented 𝑇1 that will be unstable if 𝑇2 exist and stable 𝑇1 if 𝑇2 exist. Numerical simulations by simulated to describe such temporary disease-free conditions and an endemic stable conditions.

scholarly journals Varicella zoster virus infection of highly pure terminally differentiated human neurons

2012 ◽  
Vol 19 (1) ◽  
pp. 75-81 ◽  
Author(s):  
Xiaoli Yu ◽  
Scott Seitz ◽  
Tiffany Pointon ◽  
Jacqueline L. Bowlin ◽  
Randall J. Cohrs ◽  
...  
Keyword(s):  
Virus Infection ◽  
Varicella Zoster Virus ◽  
Varicella Zoster Virus Infection ◽  
Varicella Zoster ◽  
Human Neurons

scholarly journals Persistent High Frequencies of Varicella-Zoster Virus ORF4 Protein-Specific CD4+ T Cells after Primary Infection

2006 ◽  
Vol 80 (19) ◽  
pp. 9772-9778 ◽  
Author(s):  
Louise Jones ◽  
Antony P. Black ◽  
Gathsaurie N. Malavige ◽  
Graham S. Ogg
Keyword(s):  
T Cells ◽  
Varicella Zoster Virus ◽  
Peripheral Blood ◽  
Primary Infection ◽  
Ex Vivo ◽  
High Frequencies ◽  
Varicella Zoster ◽  
Early Protein ◽  
Orf4 Protein ◽  
Ifn Γ

ABSTRACT Open reading frame 4 (ORF4) of varicella-zoster virus (VZV) encodes an immediate-early protein that is believed to be important for viral infectivity and establishing latency. Evidence suggests that VZV-specific T cells are crucial in the control of viral replication, but there are no data addressing the existence of potential ORF4 protein-specific CD4+ T cells. We tested the hypothesis that VZV ORF4 protein-specific CD4+ T cells could be identified and characterized within the peripheral blood of healthy immune donors following primary infection. Gamma interferon (IFN-γ) immunosorbent assays were used to screen peripheral blood mononuclear cells obtained from healthy seropositive donors for responses to overlapping ORF4 peptides, viral lysate, and live vaccine. High frequencies of ORF4 protein-specific T cells were detected ex vivo in individuals up to 52 years after primary infection. Several immunogenic regions of the ORF4 protein were identified, including a commonly recognized epitope which was restricted through HLA-DRB1*07. Total ORF4 protein-specific responses comprised 19.7% and 20.7% of the total lysate and vaccine responses, respectively, and were dominated by CD4+ T cells. Indeed, CD4+ T cells were found to dominate the overall virus-specific IFN-γ cellular immune response both ex vivo and after expansion in vitro. In summary, we have identified an ORF4 protein as a novel target antigen for persistent VZV-specific CD4+ T cells, with implications for disease pathogenesis and future vaccine development.

Long-Term Protective Immunity of Recipients of the OKA Strain of Live Varicella Vaccine

PEDIATRICS ◽  
1985 ◽  
Vol 75 (4) ◽  
pp. 667-671 ◽  
Author(s):  
Yoshizo Asano ◽  
Takao Nagai ◽  
Takao Miyata ◽  
Takehiko Yazaki ◽  
Shigemitsu Ito ◽  
...  
Keyword(s):  
Varicella Zoster Virus ◽  
Skin Reaction ◽  
Protective Immunity ◽  
Geometric Mean ◽  
Varicella Vaccine ◽  
Geometric Mean Titer ◽  
Positive Skin ◽  
Varicella Zoster ◽  
Mean Diameter

In spite of close contacts with patients who had varicella, 101 of 106 (95%) healthy and sick children (142 of 147 (97%) exposures of these children) who had received the OKA strain of live varicella vaccine 7 to 10 years earlier were protected against the disease completely. Among them, 37 of 38 (97%) vaccine recipients who received immunologic testing had varicella-zoster virus (VZV) antibodies tested by fluorescent antibody to membrane antigen method with a geometric mean titer of 1:9.3, and 37 of the 38 (97%) showed positive skin reaction to varicella-zoster virus antigen with erythema (mean diameter 13.4 mm). These findings were compared with those for 29 children who had contracted typical varicella 7 to 10 years earlier, whose seropositive rate was 100% with a geometric mean titer of 1:10.5, and 97% of whom (28/29) had positive skin reaction with mean diameter of 12.9 mm. These results indicate that the vaccine-induced protective immunity persists for approximately one decade and is almost equal to the long-term immunity following natural infection.

Aseptic meningitis caused by the Varicella-zoster virus after primary infection in an immunocompetent child: a case report

2018 ◽  
Vol 76 (2) ◽  
pp. 234-236
Author(s):  
Claudie Lamoureux ◽  
Charlotte Flatrès ◽  
Sophie Vallet ◽  
Adissa Tran - Minoui ◽  
Christopher Payan ◽  
...  
Keyword(s):  
Case Report ◽  
Varicella Zoster Virus ◽  
Aseptic Meningitis ◽  
Primary Infection ◽  
Varicella Zoster ◽  
Immunocompetent Child

scholarly journals Varicella Vaccine Meningitis as a Complication of Herpes Zoster in Twice-Immunized Immunocompetent Adolescents

2020 ◽  
Vol 35 (13) ◽  
pp. 889-895 ◽  
Author(s):  
Veena Ramachandran ◽  
Stephen C. Elliott ◽  
Kathie L. Rogers ◽  
Randall J. Cohrs ◽  
Miles Weinberger ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Herpes Zoster ◽  
Varicella Zoster Virus ◽  
Varicella Vaccine ◽  
The United States ◽  
Vaccine Virus ◽  
Virus Reactivation ◽  
Wild Type ◽  
Varicella Zoster ◽  
Intravenous Acyclovir

Varicella-zoster virus vaccination is recommended for virtually all young children in the United States, Canada, and several other countries. Varicella vaccine is a live attenuated virus that retains some of its neurotropic properties. Herpes zoster caused by vaccine virus still occurs in immunized children, although the rate is much lower than in children who had wild-type varicella. It was commonly thought that 2 varicella vaccinations would protect children against the most serious complication of meningitis following herpes zoster; however, 2 meningitis cases have already been published. We now report a third case of varicella vaccine meningitis and define risk factors shared by all 3 immunized adolescents. The diagnosis in cerebrospinal fluid in this third case was verified by amplifying and sequencing portions of the viral genome, to document fixed alleles found only in the vaccine strain. Viral antibody was also detected in the cerebrospinal fluid by confocal microscopy. When compared with the other 2 cases, remarkably all 3 were 14 years old when meningitis occurred. All 3 were treated with intravenous acyclovir, with complete recovery. The adolescent in our case report also had recurrent asthma, which was treated with both prednisone tablets and beclomethasone inhaler before onset of meningitis. When the 3 cases were considered together, they suggested that immunity to varicella-zoster virus may be waning sufficiently in some twice-immunized adolescents to make them vulnerable to varicella vaccine virus reactivation and subsequent meningitis. This complication rarely happens in children after wild-type varicella.

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