A Full-Genome Phylogenetic Analysis of Varicella-Zoster Virus Reveals a Novel Origin of Replication-Based Genotyping Scheme and Evidence of Recombination between Major Circulating Clades

Peters, Geoffrey A.; Tyler, Shaun; Grose, Charles; Severini, Alberto; Gray, Michael J.; Upton, Chris

doi:10.1128/jvi.00715-06

Cited by 145 publications

(186 citation statements)

References 61 publications

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“…VZV-32 is a low passage laboratory strain; its genome has been completely sequenced and falls within European clade 1 of VZV genotypes (40). Skin explants were infected with the parental rOka strain as in ref.…”

Section: Methodsmentioning

confidence: 99%

Autophagic flux without a block differentiates varicella-zoster virus infection from herpes simplex virus infection

Buckingham

Carpenter

Jackson

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Autophagy is a process by which misfolded and damaged proteins are sequestered into autophagosomes, before degradation in and recycling from lysosomes. We have extensively studied the role of autophagy in varicella-zoster virus (VZV) infection, and have observed that vesicular cells are filled with >100 autophagosomes that are easily detectable after immunolabeling for the LC3 protein. To confirm our hypothesis that increased autophagosome formation was not secondary to a block, we examined all conditions of VZV infection as well as carrying out two assessments of autophagic flux. We first investigated autophagy in human skin xenografts in the severe combined immunodeficiency (SCID) mouse model of VZV pathogenesis, and observed that autophagosomes were abundant in infected human skin tissues. We next investigated autophagy following infection with sonically prepared cell-free virus in cultured cells. Under these conditions, autophagy was detected in a majority of infected cells, but was much less than that seen after an infected-cell inoculum. In other words, inoculation with lower-titered cell-free virus did not reflect the level of stress to the VZV-infected cell that was seen after inoculation of human skin in the SCID mouse model or monolayers with higher-titered infected cells. Finally, we investigated VZVinduced autophagic flux by two different methods (radiolabeling proteins and a dual-colored LC3 plasmid); both showed no evidence of a block in autophagy. Overall, therefore, autophagy within a VZV-infected cell was remarkably different from autophagy within an HSV-infected cell, whose genome contains two modifiers of autophagy, ICP34.5 and US11, not present in VZV.V ZV induces macroautophagy (hereafter referred to as autophagy) in skin cells within the typical exanthem associated with either primary VZV infection (varicella or chickenpox) or VZV reactivation (herpes zoster or shingles). During prior studies, the extent of autophagy was gauged by enumeration of autophagosomes by both 2D and 3D microscopy (1, 2). The usual number of autophagosomes seen by 3D animation was 100 per infected cell, but sometimes approached 200 per cell. In contrast, a typical nonstressed cell usually has fewer than 4 autophagosomes (3, 4). When monolayers were inoculated with VZV-infected cells, the traditional method for VZV infection, autophagy was again easily seen after enumeration of autophagosomes and immunoblotting for the LC3-phosphatidylethanolamine conjugate (LC3-II). Again these results suggested that autophagic flux was present during VZV infection in cultured cells.As part of a more extensive assessment of autophagy after VZV-induced cellular stress, we have now investigated autophagy in infected human skin xenografts from the SCID mouse model of VZV infection. This model is the most accurate representation of the skin manifestation of varicella in the human host (5, 6). Finally, we addressed an important point about the nature of VZV-induced autophagy. Because the number of autophagosomes seen in the human vesicle...

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Section: Methodsmentioning

confidence: 99%

Autophagic flux without a block differentiates varicella-zoster virus infection from herpes simplex virus infection

Buckingham

Carpenter

Jackson

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Recent advances in high-throughput sequencing of complete viral genomes have allowed natural (field) recombination to be studied in a number of different alphaherpesviruses affecting animals and humans, including herpes simplex virus 1 (HSV-1), varicella-zoster virus (VZV) and infectious laryngotracheitis virus (ILTV) (Kolb et al, 2013;Lee et al, 2013;Norberg et al, 2015Norberg et al, , 2006Peters et al, 2006). Such studies provide insights into virus evolution and also allow the risk of recombination to be assessed in the context of attenuated vaccine use.…”

Section: Introductionmentioning

confidence: 99%

Evidence of widespread natural recombination among field isolates of equine herpesvirus 4 but not among field isolates of equine herpesvirus 1

Vaz

Horsington

Hartley

et al. 2016

Journal of General Virology

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Recombination in alphaherpesviruses allows evolution to occur in viruses that have an otherwise stable DNA genome with a low rate of nucleotide substitution. High-throughput sequencing of complete viral genomes has recently allowed natural (field) recombination to be studied in a number of different alphaherpesviruses, however, such studies have not been applied to equine herpesvirus 1 (EHV-1) or equine herpesvirus 4 (EHV-4). These two equine alphaherpesviruses are genetically similar, but differ in their pathogenesis and epidemiology. Both cause economically significant disease in horse populations worldwide. This study used highthroughput sequencing to determine the full genome sequences of EHV-1 and EHV-4 isolates (11 and 14 isolates, respectively) from Australian or New Zealand horses. These sequences were then analysed and examined for evidence of recombination. Evidence of widespread recombination was detected in the genomes of the EHV-4 isolates. Only one potential recombination event was detected in the genomes of the EHV-1 isolates, even when the genomes from an additional 11 international EHV-1 isolates were analysed. The results from this study reveal another fundamental difference between the biology of EHV-1 and EHV-4. The results may also be used to help inform the future safe use of attenuated equine herpesvirus vaccines.

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“…The direct fluorescent antibody (DFA) assay uses specific fluorescein-conjugated, polyclonal or monoclonal VZV antibodies to detect VZV antigens on slides with cells scraped from identified skin lesions [235,423,425,433,434,438,[443][444][445][446][447] , and there is also an immunoperoxidase version [348] . The monoclonal antibodies of choice are those against cell membrane-associated viral antigens [446] .…”

Section: Direct Fluorescent Antibody Assaymentioning

confidence: 99%

“…It must also be borne in mind that herpes zoster in vaccinated subjects may be due to the vaccine virus or De Paschale M et al . Microbiology laboratory in mother-child VZV infection the wild-type virus, and there also the possibility of their recombination [5,30,221,234,235] . The vaccine may also be useful in preventing varicella if administered within 3-5 d of exposure to infection due to contact, even if not entirely prevents it [5,[236][237][238] .…”

Section: Prevention and Treatmentmentioning

confidence: 99%

Microbiology laboratory and the management of mother-child varicella-zoster virus infection

Paschale

Clerici

2016

WJV

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Varicella-zoster virus, which is responsible for varicella (chickenpox) and herpes zoster (shingles), is ubiquitous and causes an acute infection among children, especially those aged less than six years. As 90% of adults have had varicella in childhood, it is unusual to encounter an infected pregnant woman but, if the disease does appear, it can lead to complications for both the mother and fetus or newborn. The major maternal complications include pneumonia, which can lead to death if not treated. If the virus passes to the fetus, congenital varicella syndrome, neonatal varicella (particularly serious if maternal rash appears in the days immediately before or after childbirth) or herpes zoster in the early years of life may occur depending on the time of infection. A Microbiology laboratory can help in the diagnosis and management of mother-child infection at four main times: (1) when a pregnant woman has been exposed to varicella or herpes zoster, a prompt search for specific antibodies can determine whether she is susceptible to, or protected against infection; (2) when a pregnant woman develops clinical symptoms consistent with varicella, the diagnosis is usually clinical, but a laboratory can be crucial if the symptoms are doubtful or otherwise unclear (atypical patterns in immunocompromised subjects, patients with post-vaccination varicella, or subjects who have received immunoglobulins), or if there is a need for a differential diagnosis between varicella and other types of dermatoses with vesicle formation; (3) when a prenatal diagnosis of uterine infection is required in order to detect cases of congenital varicella syndrome after the onset of varicella in the mother; and (4) when the baby is born and it is necessary to confirm a diagnosis of varicella (and its complications), make a differential diagnosis between varicella and other diseases with similar symptoms, or confirm a causal relationship between maternal varicella and malformations in a newborn. Core tip: Although varicella during pregnancy is infrequent and congenital varicella syndrome (CVS) is rare, every available means should be used to prevent and diagnose them. Microbiology laboratories can be crucial in these situations: Evaluating a mother's immune status with sensitive and specific tests for the detection of antibodies; allowing a rapid diagnosis with molecular biology tests when a clinical manifestation may be due to different etiologies; following pregnant women with varicella for the prenatal diagnosis of CVS with close collaboration between molecular biology investigators and specialists in imaging diagnostics.De Paschale M, Clerici P. Microbiology laboratory and the management of mother-child varicella-zoster virus infection. World

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A Full-Genome Phylogenetic Analysis of Varicella-Zoster Virus Reveals a Novel Origin of Replication-Based Genotyping Scheme and Evidence of Recombination between Major Circulating Clades

Cited by 145 publications

References 61 publications

Autophagic flux without a block differentiates varicella-zoster virus infection from herpes simplex virus infection

Autophagic flux without a block differentiates varicella-zoster virus infection from herpes simplex virus infection

Evidence of widespread natural recombination among field isolates of equine herpesvirus 4 but not among field isolates of equine herpesvirus 1

Microbiology laboratory and the management of mother-child varicella-zoster virus infection

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