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A A Gershon

Publications and source records attributed to A A Gershon.

At least 19 recordsLinked to original sources
PubMed1998

Aberrant intracellular localization of Varicella-Zoster virus regulatory proteins during latency.

Varicella-Zoster virus (VZV) is a herpesvirus that becomes latent in sensory neurons after primary infection (chickenpox) and subsequently may reactivate to cause zoster. The mechanism by which this virus maintains latency, and the factors involved, are poorly understood. Here we demonstrate, by immunohistochemical analysis of ganglia obtained at autopsy from seropositive patients without clinical symptoms of VZV infection that viral regulatory proteins are present in latently infected neurons. These proteins, which localize to the nucleus of cells during lytic infection, predominantly are detected in the cytoplasm of latently infected neurons. The restriction of regulatory proteins from the nucleus of latently infected neurons might interrupt the cascade of virus gene expression that leads to a productive infection. Our findings raise the possibility that VZV has developed a novel mechanism for maintenance of latency that contrasts with the transcriptional repression that is associated with latency of herpes simplex virus, the prototypic alpha herpesvirus.

Aged↗
PubMed1998

Congenital varicella-zoster virus infection and Barrett's esophagus.

Congenital varicella syndrome is a rare complication of varicella-zoster virus (VZV) infection during pregnancy. An infant was exposed to VZV at 18.5 weeks of gestation and had eye and skin abnormalities at birth and persistent feeding difficulties, prompting esophageal biopsies at 12 days and 20 and 20.5 months of age. Esophageal tissues demonstrated specialized intestinal metaplasia (Barrett's esophagus). VZV DNA (in situ hybridization) and proteins (immunohistochemistry and polymerase chain reaction) were found in esophageal epithelial cells adjacent to the Barrett's lesion. Immediate-early 63 protein (IE63) of VZV was demonstrated in the day 12 specimen, and IE62 and the late VZV glycoprotein E (gE) were found in the 20-month specimen. Clinical and endoscopic improvement followed fundoplication and acyclovir therapy, but VZV DNA and IE62 persisted in esophageal tissue. These findings associate VZV with specialized intestinal metaplasia within the esophagus and suggest a novel site for either latent or active VZV infection.

Barrett Esophagus↗
PubMed1998

Varicella vaccine.

Explore the source record for details and available documents.

Chickenpox Vaccine↗
PubMed1997

Varicella-zoster virus infection in children with underlying human immunodeficiency virus infection.

This article describes a prospective longitudinal study of varicella-zoster virus (VZV) infections in human immunodeficiency virus (HIV)-infected children, designed to determine their natural history of VZV infection and possible effects of VZV on the progression of HIV infection. Varicella was usually not a serious acute problem, and it did not seem to precede clinical deterioration. The rate of zoster was high: 70% in children with low levels of CD4+ lymphocytes at the time of development of varicella. It is predicted that immunization with live attenuated varicella vaccine is unlikely to be deleterious to HIV-infected children. Moreover, if they are immunized when they still have relatively normal levels of CD4+ lymphocytes, they may have a lower rate of reactivation of VZV than if they were allowed to develop natural varicella when their CD4+ cell counts have fallen to low levels as a result of progressive HIV infection.

Antibodies, Viral↗
PubMed1997

Quality standards for immunization. Guidelines from the Infectious Diseases Society of America.

This is the third in a series of guidelines commissioned by the Infectious Diseases Society of America through its Practice Guidelines Committee. It is presented as a standard of care rather than a practice guideline because the case for following these recommendations is very strong and it should be followed with rare exceptions. The purpose of this guideline is to provide assistance to clinicians when making decisions on providing immunizations to healthy infants, children, and adults. The document is a summary of guidelines already developed by national organizations. The targeted providers are pediatricians, family practitioners, internists, and other physicians who provide immunizations. The IDSA provided the funding. Panel members represent experts in adult and pediatric infectious diseases. The guidelines are evidence-based. A standard ranking system is used for the strength of the recommendations and the quality of the evidence cited in the literature reviewed. The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council. An executive summary and tables highlight the major recommendations. Indicators for measuring compliance with the standards are included.

Adolescent↗
PubMed1996

The varicella vaccine. Clinical trials in immunocompromised individuals.

A review of the use of live attenuated varicella vaccine in immunocompromised children, particularly those with underlying leukemia in remission, is presented. Data concerning safety, immunogenicity, and efficacy of this vaccine in high-risk children are reviewed. The unique contributions toward our understanding of varicella vaccine, including spread of vaccine-type virus, incidence of zoster, and immune correlates provided by studies of immunocompromised patients are discussed. The importance of protecting high-risk children against severe varicella by the use of varicella vaccine is apparent.

Canada↗
PubMed1996

The protective effect of immunologic boosting against zoster: an analysis in leukemic children who were vaccinated against chickenpox.

Whether reexposure of varicella-immune persons to varicella-zoster virus would protect against or predispose to development of zoster was analyzed. The rate of zoster in 511 leukemic recipients of varicella vaccine who had 1 or > 1 dose of varicella vaccine and in those who did or did not have a household exposure to varicella was determined. A Kaplan-Meier life-table analysis revealed that the incidence of zoster was lower in those given > 1 dose of vaccine (P < .05). A Cox proportional hazards analysis showed that both household exposure to varicella and receipt of > 1 dose of vaccine were highly protective (P < .01) against zoster. Thus, the risk of zoster is decreased by reexposure to varicella-zoster virus, either by vaccination or by close exposure to varicella.

Chickenpox↗
PubMed1996

Varicella vaccine for immunocompromised children: results of collaborative studies in the United States and Canada.

Varicella vaccine in immunocompromised children was clinically evaluated in 575 US and Canadian children with leukemia in remission by the Varicella Vaccine Collaborative Study. Most children had chemotherapy stopped 1 week before and 1 week after immunization. Steroids were stopped for 3 weeks (1 week before to 2 weeks after vaccination). Varicella vaccine was safe, immunogenic, and effective in leukemic children at risk for serious disease or death from chickenpox. The major side effect was mild rash in 50% approximately 1 month after immunization. About 40% of children who developed rash were treated with acyclovir. Vaccine efficacy was judged by the degree of protection after a household exposure to varicella; of 123 exposed children, 17 (14%) developed a mild form of varicella. The vaccine protected completely against severe varicella. Leukemic vaccines were less likely to develop zoster than were comparable children with leukemia who had wild type varicella. Thus, varicella vaccine, administered carefully with close follow-up, is extremely beneficial for leukemic children.

Canada↗
PubMed1996

Targeting of glycoprotein I (gE) of varicella-zoster virus to the trans-Golgi network by an AYRV sequence and an acidic amino acid-rich patch in the cytosolic domain of the molecule.

Previous studies suggested that varicella-zoster virus (VZV) envelope glycoproteins (gps) are selectively transported to the trans-Golgi network (TGN) and that the cytosolic domain of gpI (gE) targets it to the TGN. To identify targeting signals in the gpI cytosolic domain, intracellular protein trafficking was studied in transfected cells expressing chimeric proteins in which a full-length or mutated gpI cytosolic domain was fused to the gpI transmembrane domain and interleukin-2 receptor (tac) ectodomain. Expressed protein was visualized with antibodies to tac. A targeting sequence (AYRV) and a second, acidic amino acid-rich region of the gpI cytosolic domain (putative signal patch) were each sufficient to cause expressed protein to colocalize with TGN markers. This targeting was lost when the tyrosine of the AYRV sequence was replaced with glycine or lysine, when arginine was replaced with glutamic acid, or when valine was substituted with lysine. In contrast, tyrosine could be replaced by phenylalanine and valine could be substituted with leucine. Mutation of alanine to aspartic acid or deletion of alanine abolished TGN targeting. Exposure of transfected cells to antibodies to the tac ectodomain revealed that the TCN targeting of expressed tac-gpI chimeric proteins occurred as a result of selective retrieval from the plasmalemma. These data suggest that the AYRV sequence and a second signaling patch in the cytosolic domain of gpI are responsible for its targeting to the TGN. The observations also support the hypothesis that the TGN plays a critical role in the envelopment of VZV.

Amino Acid Sequence↗
PubMed1996

Live attenuated varicella vaccine.

Varicella-zoster virus (VZV) is a ubiquitous human pathogen that causes varicella, commonly called chicken pox; establishes latency; and reactivates as herpes zoster, referred to as shingles. A live attenuated varicella vaccine, derived from the Oka strain of VZV has clinical efficacy for the prevention of varicella. The vaccine induces persistent immunity to VZV in healthy children and adults. Immunization against VZV also has the potential to lower the risk of reactivation of latent virus. The varicella vaccine may eventually reduce or eliminate herpes zoster, which is a serious problem for elderly and immunocompromised individuals.

Adult↗
PubMed1996

Epidemiology and management of postherpetic neuralgia.

Herpes zoster occurs rarely in immunocompetent children and infrequently in immunocompetent young adults. However, its incidence increases with age, particularly after age 50. Reactivation of varicella-zoster virus (VZV) is characterized by a rash and is generally accompanied by considerable pain, dysesthesias, and skin hypersensitivity. Chronic pain that is sometimes experienced after the rash has healed is referred to as postherpetic neuralgia (PHN), the most common complication of herpes zoster. Postherpetic neuralgia is often severe and, unfortunately, refractory to most forms of treatment. The incidence of PHN also increases dramatically with increased age. More than 50% of zoster patients over 60 years old will develop PHN, which may persist for months and even years. Thus, established PHN is difficult to manage, often causing serious morbidity, depression, and high costs in terms of consumption of healthcare resources. Currently, early antiviral treatment with famciclovir has shown promise of reducing the duration of PHN.

Adult↗
PubMed1995

Infection of cells by varicella zoster virus: inhibition of viral entry by mannose 6-phosphate and heparin.

Envelope glycoproteins of varicella zoster virus (VZV) contain mannose 6-phosphate (Man6P) residues. We now report that Man6P competitively and selectively inhibits infection of cells in vitro by cell-free VZV; furthermore, dephosphorylation of VZV by exposure to alkaline phosphatase rapidly destroys infectivity. Cells are also protected from VZV in a concentration-dependent manner by heparin (ED50 = 0.23 micrograms/ml; 95% confidence limits = 0.16-0.26 microgram/ml) but not by chondroitin sulfate. Both heparin and Man6P are protective only when present about the time of inoculation. Heparin but not Man6P interferes with the attachment of VZV to cell surfaces; moreover, VZV binds to heparin-affinity columns. These data are compatible with a working hypothesis, whereby VZV attaches to cell surfaces by binding to a heparin sulfate proteoglycan. This binding stabilizes VZV, making possible a low-affinity interaction with another Man6P-dependent receptor, which is necessary for viral entry.

Alkaline Phosphatase↗
PubMed1995

Present and future challenges of immunizations on the health of our patients.

A recent analysis demonstrated a change in incidence approaching 100% for diseases against which we routinely immunize in the United States. At present, measles, mumps, rubella, invasive Haemophilus disease, poliomyelitis, diphtheria and tetanus are well-controlled but not eliminated. Diseases that now pose special problems include pertussis, hepatitis A and B and varicella. The incidence of pertussis surged in 1994, possibly in part because of waning immunity in the immunized population. Acellular pertussis vaccines are available for booster doses in children but are not now recommended for adults. Licensure of acellular pertussis vaccines for primary immunization of infants is eagerly awaited. Recombinant hepatitis B vaccine has been licensed for more than 10 years but there has been little change in disease incidence in the United States. Routine immunization of infants is now recommended but concerns exist about cost and persistence of immunity into adolescence. Inactivated hepatitis A vaccines appear to be highly effective in preventing clinical hepatitis and controlling epidemics. Potential target populations include military personnel, day-care attendees and travelers. Hepatitis A vaccine may be recommended for all children after approval by the United States Food and Drug Administration and if a combination vaccine becomes available. A live, attenuated varicella vaccine developed in 1974 and unlicensed in the United States is safe and highly effective in preventing varicella in healthy and immunocompromised populations. It also appears to reduce subsequent development of herpes zoster. Vaccines against pneumococci (conjugate vaccine), respiratory syncytial virus, rotavirus, tuberculosis and human immunodeficiency virus are needed. Research and technology to develop these vaccines must be developed, and efficient delivery mechanisms must be created and implemented.

Child↗
PubMed1995

Envelopment of varicella-zoster virus: targeting of viral glycoproteins to the trans-Golgi network.

Previous studies suggested that varicella-zoster virus derives its final envelope from the trans-Golgi network (TGN) and that envelope glycoproteins (gps) are transported to the TGN independently of nucleocapsids. We tested the hypothesis that gpI is targeted to the TGN as a result of a signal sequence or patch encoded in its cytosolic domain. cDNAs encoding gpI wild type (wt) and a truncated mutant gpI(trc) lacking transmembrane and cytosolic domains were cloned by using the PCR. Cells transfected with cDNA encoding gpI(wt) or gpI(trc) synthesized and N glycosylated the proteins. gpI(wt) accumulated in the TGN, some reached the plasmalemma, but none was secreted. In contrast, gpI(trc) was retained and probably degraded in the endoplasmic reticulum; none was found on cell surfaces, but some was secreted. The distribution of gpI(trc) was not affected by deletion of potential glycosylation sites. To locate a potential gpI-targeting sequence, cells were transfected with cDNA encoding chimeric proteins in which the ectodomain of a plasmalemmal marker, the interleukin-2 receptor (tac), was fused to different domains of gpI. A chimeric protein in which tac was fused with the transmembrane and cytoplasmic domains of gpI was targeted to the TGN. In contrast, a chimeric protein in which tac was fused only with the gpI transmembrane domain passed through the TGN and concentrated in endosomes. We conclude that gpI is targeted to the TGN as a result of a targeting sequence or patch in its cytosolic domain.

Animals↗
PubMed1995

Varicella-zoster virus: prospects for control.

There have been a number of new developments in the field of VZV concerning pathogenesis, diagnosis, prevention, and treatment. These include improved understanding of how latent infection develops and is maintained, the development and, we hope, licensure of live attenuated varicella vaccine for routine use in children and in adults who have not had varicella, an increased availability of antiviral therapy for healthy and immunocompromised patients, and the development of newer diagnostic techniques, including PCR to diagnose illnesses caused by VZV and LA for rapid, sensitive, and accurate determination of immune status to VZV. Even as vaccine use becomes more and more widespread, we will continue to need effective antiviral therapy for VZV for use in immunocompromised persons and in those in whom zoster develops. Eventually it may be possible to develop either a vaccine or an antiviral drug that prevents the development of latent VZV infection. Until that time, however, VZV will remain with us, and we will continue to need an effective antiviral armamentarium, including diagnostic techniques, passive immunization, antiviral therapy, and vaccine.

Adult↗