Comparative Evaluation of AmpliVue HSV 1+2 Assay with ELVIS Culture for Detecting Herpes Simplex Virus 1 (HSV-1) and HSV-2 in Clinical Specimens
Paul A. GranatoBrenda R. AlkinsBelinda Yen‐LiebermanWallace GreeneJessica ConnollyBlake W. BuchanNathan A. Ledeboer
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Abstract:
The AmpliVue HSV 1+2 assay was compared to the ELVIS HSV ID and D(3) Typing Culture System for the qualitative detection and differentiation of herpes simplex virus 1 (HSV-1) and HSV-2 DNA in 1,351 cutaneous and mucocutaneous specimens. Compared to ELVIS, AmpliVue had sensitivities of 95.7 and 97.6% for detecting HSV-1 and HSV-2, respectively. Following arbitration of discordant results by an independent molecular method, the AmpliVue assay had a resolved sensitivity and specificity of 99.2 and 99.7%, respectively, for both HSV-1 and HSV-2, whereas ELVIS had a resolved sensitivity of 87.1% for HSV-1 and 84.5% for HSV-2.Keywords:
HSL and HSV
Mucocutaneous zone
Alphaherpesvirinae
Simplexvirus
Ο HSV-1 είναι ένας DNA ιός που ανήκει στην οικογένεια των ερπητοϊών (Herpesviridae) και συγκεκριμένα στην οικογένεια των α-ερπητοϊών (Alphaherpesvirinae). Είναι νευροτρόπος ιός ο οποίος πραγματοποιεί λυτικό κύκλο στα επιθηλιακά κύτταρα ενώ στα νευρικά κύτταρα βρίσκεται σε λανθάνουσα φάση. Ο λυτικός κύκλος του HSV-1 λαμβάνει χώρα σε τρεις φάσεις, την άμεσα πρώιμη (α), την πρώιμη (β) και την όψιμη(γ) και αποτελεί χαρακτηριστικό τρόπο έκφρασης των γονιδίων των ερπητοϊών. Στα πλαίσια της παρούσας διδακτορικής διατριβής διερευνήθηκαν μηχανισμοί που διέπουν την μόλυνση από τον ιό του απλού έρπητα τύπου Ι (HSV-1). Συγκεκριμένα, διερευνήθηκε η δράση του CD40L και ο ρόλος του στην έκβαση της μόλυνσης από τον HSV-1. Επιπλέον, διερευνήθηκε το πρότυπο μεθυλίωσης κυτταρικών γονιδίων σε διάφορα στάδια της μόλυνσης από τον ιό.Ως προς το πρώτο σκέλος της εργασίας, κατά την οποία διερευνήθηκε η δράση του CD40L στην μόλυνση από τον HSV-1, βρέθηκε ότι ο CD40L παρεμποδίζει την εξέλιξη της μόλυνσης άμεσα, μετά την είσοδο του ιού στο κύτταρο. Μελετήθηκαν διάφορα στάδια της μόλυνσης καθώς κ αντιϊκοί μηχανισμοί ενώ έμφαση δόθηκε στον μηχανισμό της αυτοφαγίας. Συνολικά, ο ιός παρεμποδίζεται από την ενεργοποίηση του μονοπατιού του CD40L μέσω ενός μηχανισμού που σχετίζεται με την κινάση PI3K και είναι ανεξάρτητος της αυτοφαγίας.Ως προς το δεύτερο σκέλος της διατριβής, μελετήθηκε το πρότυπο μεθυλίωσης του κυτταρικού γονιδιώματος σε λυτική κ λανθάνουσα μόλυνση με τον ιό HSV-1 δίνοντας ιδιαίτερη έμφαση στο πρότυπο μεθυλίωσης γονιδίων που κωδικοποιούν για ένζυμα που σχετίζονται με επιγενετικά φαινόμενα. Βρέθηκε ότι στην άμεσα πρώιμη κ πρώιμη φάση του λυτικού κύκλου υπάρχει έντονη διακύμανση των επιπέδων μεθυλίωσης των κυτταρικών γονιδίων ενώ στην όψιμη φάση της μόλυνσης και κατά τη λανθάνουσα κατάσταση το πρότυπο μεθυλίωσης είναι διαφορετικό από την κατάσταση ηρεμίας αλλά σταθερό.
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Human herpesvirus (Herpes simplex virus type 1; HSV-1) and Human herpesvirus 2 (Herpes simplex virus type 2; HSV-2) are members of the Herpesviridae, subfamily Alphaherpesvirinae, genus Simplexvirus. The viruses are characterised by a short (18–24 h) replicative cycle that is cytolytic. Humans are the only natural host, although a wide range of primates and non-primates can be infected under artificial (laboratory) conditions. The genomes of HSV-1 and HSV-2 show considerable homology (∼50%) but HSV-1 and HSV-2 are biologically and antigenically distinct. Infection with either virus may be clinically inapparent or may produce symptoms that range from the mild and trivial to those of severe disease. During infection this virus establishes latency in the nuclei of nerve cells in the local dorsal root ganglion. At intervals throughout the life of the host the virus may reactivate and is either shed silently or produces symptoms of recurrent infection. In immunocompromised individuals both primary infection and recurrent infection may be severe and life threatening.
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The AmpliVue HSV 1+2 assay was compared to the ELVIS HSV ID and D(3) Typing Culture System for the qualitative detection and differentiation of herpes simplex virus 1 (HSV-1) and HSV-2 DNA in 1,351 cutaneous and mucocutaneous specimens. Compared to ELVIS, AmpliVue had sensitivities of 95.7 and 97.6% for detecting HSV-1 and HSV-2, respectively. Following arbitration of discordant results by an independent molecular method, the AmpliVue assay had a resolved sensitivity and specificity of 99.2 and 99.7%, respectively, for both HSV-1 and HSV-2, whereas ELVIS had a resolved sensitivity of 87.1% for HSV-1 and 84.5% for HSV-2.
HSL and HSV
Mucocutaneous zone
Alphaherpesvirinae
Simplexvirus
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Citations (18)
Since the onset of the COVID-19 outbreak, numerous articles have highlighted a possible link between COVID-19 vaccination or infection and Herpesviridae co-infection or reactivation. The authors conducted an exhaustive literature review on this topic, the results of which are presented individually for each member of the Herpesviridae family: Herpes Simplex Virus (HSV) types-1 (HSV-1) and 2 (HSV-2); Varicella-Zoster Virus (VZV); Epstein-Barr Virus (EBV); Cytomegalovirus (CMV); HHV-6; HHV-7; and HHV-8. These human herpesviruses can serve as prognostic markers for the COVID-19 infection and may even underlie some of the clinical manifestations initially attributed to SARS-CoV-2. In addition to SARS-CoV-2 infection, all corresponding vaccines approved to date in Europe appear capable of inducing herpesvirus reactivation. It is important to consider all viruses of the Herpesviridae family when managing patients infected with or recently vaccinated against COVID-19.
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Clinical observations indicate that herpes simplex virus type 1 (HSV-1) is significantly less likely than herpes simplex virus type 2 (HSV-2) to establish latency in (or reactivate from) sacral ganglionic tissue. In an effort to identify viral functions associated with latency, we analyzed HSV-1 isolates from three patients with established recurrent genital herpes and sought evidence of DNA sequences and proteins similar to those found in HSV-2. By restriction endonuclease cleavage patterns and by DNA hybridization analysis using either whole HSV-2 DNA or several cloned segments of HSV-2 DNA as probes, we found that the three HSV-1 isolates from patients with recurrent genital herpes showed no unusual homology to HSV-2 as compared with other HSV-1 isolates. Similarly, the proteins of these isolates could not be distinguished from those of other HSV-1 isolates and were distinct from those of HSV-2. At this level of resolution, there was no evidence to suggest that these recurrent genital HSV-1 isolates were intertypic recombinants, nor did they show any other unusual similarity to HSV-2.
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