Evidence map›Paper›PMID 17459924›Full record

ArticleJournal of virology2007

Diverse herpes simplex virus type 1 thymidine kinase mutants in individual human neurons and Ganglia.

Kening Wang, Gowtham Mahalingam, Susan E Hoover, Erik K Mont, Steven M Holland, Jeffrey I Cohen, Stephen E Straus

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 43 citations in OpenAlex.

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  19. Novel aspects of corneal angiogenic and lymphangiogenic privilege.Progress in retinal and eye research · 2010
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Kening WangMedical Virology Section, Laboratory of Clinical Infectious Disease, NIAID/NIH, Building 10, Room 11N-234, 10 Center Dr., Bethesda, MD 20892, USA. kwang@niaid.nih.gov
Gowtham Mahalingam
Susan E Hoover
Erik K Mont
Steven M Holland
Jeffrey I Cohen
Stephen E Straus
Organogenesis (United States) · USNational Institute of Allergy and Infectious Diseases · US

Funding

Genes And Gene Products As ImmunoadjuvantsZIAAI000647 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI HOLLAND, STEVEN · 2009 to 2025
$22.6M
Transgenic Animal Models Of Human Immune DefectsZIAAI000646 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI HOLLAND, STEVEN · 2009 to 2025
$22.2M
Pathogenesis and Chemotherapy of Human Virus InfectionsZIAAI000058 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI COHEN, JEFFREY · 2009 to 2025
$8.8M
GENES AND GENE PRODUCTS AS IMMUNOADJUVANTSZ01AI000647 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI HOLLAND, STEVEN M · 1992 to 2008
$5.4M
TRANSGENIC ANIMAL MODELS OF HUMAN IMMUNE DEFECTSZ01AI000646 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI HOLLAND, STEVEN M · 1992 to 2008
$2.4M
THE PATHOGENESIS AND CHEMOTHERAPY OF HERPESVIRUS INFECTIONS IN MANZ01AI000058 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI COHEN, JEFFREY · 1985 to 2008
$680k
Intramural NIH HHS
6 · The paper itself

Abstract

Mutations in the thymidine kinase gene (tk) of herpes simplex virus type 1 (HSV-1) explain most cases of virus resistance to acyclovir (ACV) treatment. Mucocutaneous lesions of patients with ACV resistance contain mixed populations of tk mutant and wild-type virus. However, it is unknown whether human ganglia also contain mixed populations since the replication of HSV tk mutants in animal neurons is impaired. Here we report the detection of mutated HSV tk sequences in human ganglia. Trigeminal and dorsal root ganglia were obtained at autopsy from an immunocompromised woman with chronic mucocutaneous infection with ACV-resistant HSV-1. The HSV-1 tk open reading frames from ganglia were amplified by PCR, cloned, and sequenced. tk mutations were detected in a seven-G homopolymer region in 11 of 12 ganglia tested, with clonal frequencies ranging from 4.2 to 76% HSV-1 tk mutants per ganglion. In 8 of 11 ganglia, the mutations were heterogeneous, varying from a deletion of one G to an insertion of one to three G residues, with the two-G insertion being the most common. Each ganglion had its own pattern of mutant populations. When individual neurons from one ganglion were analyzed by laser capture microdissection and PCR, 6 of 14 HSV-1-positive neurons were coinfected with HSV tk mutants and wild-type virus, 4 of 14 were infected with wild-type virus alone, and 4 of 14 were infected with tk mutant virus alone. These data suggest that diverse tk mutants arise independently under drug selection and establish latency in human sensory ganglia alone or together with wild-type virus.

Indexed as

Point MutationAcyclovirAntiviral AgentsDrug Resistance, ViralGanglia, SpinalHerpes SimplexHerpesvirus 1, HumanHumansNeurons, AfferentThymidine KinaseTrigeminal NucleiViral ProteinsVirus LatencyAcyclovirAntiviral AgentsThymidine KinaseViral Proteins

Identifiers

PMID17459924
PMCPMC1933309
OpenAlexW2169694960

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.