Performance of a Commercial, Type-Specific Enzyme-Linked Immunosorbent Assay for Detection of Herpes Simplex Virus Type 2-Specific Antibodies in Ugandans

Laeyendecker, Oliver; Henson, Charla; Gray, Ronald H.; Nguyen, Ruby H.N.; Horne, Bobbi Jo; Wawer, Maria J.; Serwadda, David; Kiwanuka, Noah; Morrow, Rhoda Ashley; Hogrefe, Wayne; Quinn, Thomas C.

doi:10.1128/jcm.42.4.1794-1796.2004

Cited by 61 publications

(60 citation statements)

References 13 publications

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“…Positively selected amino acid residues were frequently identi- fied in HSV glycoproteins, with the highest number of positively selected sites occurring in gC-1 and gG-2. This finding, along with the detection of five or more positively selected sites in gG-2 and a high number of nonsynonymous substitutions, was an indication that perhaps nucleotide variation and the resulting antigenic variation were impacting the sensitivity or specificity of the Western blot assay in East Africa, where there is a significant difference between ELISA and Western blot results (25)(26)(27)(28). This may be due in part to the U.S. strain of HSV-2 used to provide the antigens in the Western blot and extends to the antigen used in commercial ELISAs.…”

Section: Discussionmentioning

confidence: 99%

“…Because serology tests used to discriminate HSV-1 and HSV-2 infections are frequently inaccurate in East African populations (25)(26)(27)(28), we further examined HSV-2 gG amino acid sequences using phylogenetic methods. The analysis demonstrated that most global strains were dispersed around the tree, with few clusters with bootstrap support greater than 50%; however, there was one large (14 sequences), low-diversity clade (Ͻ0.1%) with moderate bootstrap support (Ͼ60%) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Importantly, HSV glycoproteins, in particular gG, are the target of antibody detection assays used for the diagnosis of HSV-1 or HSV-2 infections (23); therefore, a comparison of HSV-1 and HSV-2 glycoproteins could show why these tests sometimes fail, especially in East Africa, where some serological tests have an assay specificity as low as 50.7% (24)(25)(26)(27)(28). We analyzed all putative glycoprotein genes in the U L and U S regions, which included sequences derived from North America, Europe, Asia, the Republic of South Africa, and East Africa.…”

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confidence: 99%

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Global Diversity within and between Human Herpesvirus 1 and 2 Glycoproteins

Lamers¹,

Newman

Laeyendecker

et al. 2015

J Virol

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Human herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) are large-genome DNA viruses that establish a persistent infection in sensory neurons and commonly manifest with recurring oral or genital erosions that transmit virus. HSV encodes 12 predicted glycoproteins that serve various functions, including cellular attachment, entry, and egress. Glycoprotein G is currently the target of an antibody test to differentiate HSV-1 from HSV-2; however, this test has shown reduced capacity to differentiate HSV strains in East Africa. Until the recent availability of 26 full-length HSV-1 and 36 full-length HSV-2 sequences, minimal comparative information was available for these viruses. In this study, we use a variety of sequence analysis methods to compare all available sequence data for HSV-1 and HSV-2 glycoproteins, using viruses isolated in Europe, Asia, North America, the Republic of South Africa, and East Africa. We found numerous differences in diversity, nonsynonymous/synonymous substitution rates, and recombination rates between HSV-1 glycoproteins and their HSV-2 counterparts. Phylogenetic analysis revealed that while most global HSV-2 glycoprotein G sequences did not form clusters within or between continents, one clade (supported at 60.5%) contained 37% of the African sequences analyzed. Accordingly, sequences from this African subset contained unique amino acid signatures, not only in glycoprotein G, but also in glycoproteins I and E, which may account for the failure of sensitive antibody tests to distinguish HSV-1 from HSV-2 in some African individuals. Consensus sequences generated in the study can be used to improve diagnostic assays that differentiate HSV-1 from HSV-2 in global populations. IMPORTANCEHuman herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) are large DNA viruses associated with recurring oral or genital erosions that transmit virus. Up to 12 HSV-1 and HSV-2 glycoproteins are involved in HSV cell entry or are required for viral spread in animals, albeit some are dispensable for replication in vitro. The recent availability of comparable numbers of full-length HSV-1 and HSV-2 sequences enabled comparative analysis of gene diversity of glycoproteins within and between HSV types. Overall, we found less glycoprotein sequence diversity within HSV-2 than within the HSV-1 strains studied, while at the same time, several HSV-2 glycoproteins were evolving under less selective pressure. Because HSV glycoproteins are the focus of antibody tests to detect and differentiate between infections with the two strains and are constituents of vaccines in clinical-stage development, these findings will aid in refining the targets for diagnostic tests and vaccines. H erpes simplex virus 1 and 2 (HSV-1 and HSV-2) are members of the subfamily Alphaherpesvirinae. They are large, enveloped DNA viruses that cause infections that cycle between a replication stage, where infectious virus particles are shed through mucocutaneous erosions, and a latent infection stage, where the virus persists in sensory neurons (1)...

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Section: Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Global Diversity within and between Human Herpesvirus 1 and 2 Glycoproteins

Lamers¹,

Newman

Laeyendecker

et al. 2015

J Virol

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“…For example, the FDAapproved and widely available HerpeSelect enzyme-linked immunosorbent assay (ELISA) (Focus Technologies) has a high sensitivity and specificity, ranging from 96 to 100%, against the reference HSV-2 Western blot (WB) assay for testing of sera from North American or Western European populations but significantly lower specificity for testing of sera from adult African populations (2,7,16). Moreover, concordance between WB and HerpeSelect assays was found to vary between countries in sub-Saharan Africa (2,6,7,9) and according to human immunodeficiency virus (HIV) serostatus (16). HerpeSelect and other assays were compared in an evaluation study using African sera from population-based surveys, and the Kalon gG2-specific ELISA (Kalon Biologicals) was found to be as sensitive as and more specific than HerpeSelect, with WB as the reference method (16).…”

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Performance of HerpeSelect and Kalon Assays in Detection of Antibodies to Herpes Simplex Virus Type 2

et al. 2008

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“…The results are reported according to their antibody index (AI), with values of Ͻ0.9 considered negative, 0.9 to 1.0 equivocal, and Ͼ1.0 positive. Serum samples were tested in parallel using the HerpeSelect gG2 ELISA, and the results were expressed using AIs of 1.1, as recommended by the manufacturer, and 3.5, as recommended by many authors to improve the assay's specificity in African individuals (4,6,7,9,15). The kappa statistic was used to assess the concordance between the two assays.…”

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confidence: 99%