Lone Star Virus Infection

Infectious Disease Show in embeddings browser Viral Infection

This is a provisional record for one published human observation associated with Lone Star virus. The report concerned an immunocompromised adult with fatal meningoencephalitis, but etiologic attribution remains uncertain: an initial cerebrospinal-fluid detection was reproduced only at the originating laboratory and was not reproduced by later testing at a second laboratory; additional confirmation was negative. The record does not define a general clinical spectrum, established human transmission route, diagnostic case definition, or established causal disease entity.

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1
Phenotypes
1
Hypotheses
2
Gaps
5
References
1
Deep Research

Mechanistic Hypotheses

1
Lone Star virus etiologic attribution in the reported case
lsv_etiologic_attribution EMERGING
Evidence balance 1 support 1 refute
Lone Star virus may have caused or contributed to the reported fatal meningoencephalitis, but the detection was reproduced only at the originating laboratory and is insufficient to establish causality; later testing at a second laboratory did not confirm it.
Show evidence (2 references)
PMID:39983710 SUPPORT Human Clinical
"CSF mNGS testing, which we performed twice on a hospital day 3 sample, was positive for Lone star virus (LSV)."
Records the initial observation supporting an LSV association in the reported case without treating it as proof of etiology.
PMID:39983710 REFUTE Human Clinical
"Additional testing of residual CSF by CDC did not detect reads from LSV on mNGS, and confirmatory testing with viral isolation and plaque reduction neutralization testing was negative."
The non-reproduced result and negative additional confirmation weaken a definitive etiologic interpretation.
?

Discussions and Knowledge Gaps

2
Did Lone Star virus cause the fatal meningoencephalitis in the single reported human observation?
INTERPRETATION OPEN lsv_etiologic_attribution_uncertainty
The initial result supports an association, but later testing at a second laboratory did not reproduce it and other confirmation was negative. The source itself cautions that molecular detection alone does not establish causality in a highly susceptible host. Independent human observations and reproducible confirmation would be needed before asserting a causal entity or a broader clinical spectrum.
Show evidence (2 references)
PMID:39983710 SUPPORT Human Clinical
"Because mNGS is a molecular detection technique and positive testing alone is insufficient to fulfill Koch’s postulates (23), caution is warranted with clinical interpretation of mNGS results, especially with detection of a novel agent of unclear pathogenicity in highly susceptible..."
The authors explicitly limit the causal interpretation of the positive molecular result.
PMID:39983710 SUPPORT Human Clinical
"Additional testing of residual CSF by CDC did not detect reads from LSV on mNGS, and confirmatory testing with viral isolation and plaque reduction neutralization testing was negative."
Documents the unresolved discordant confirmation.
Can currently available nonhuman studies establish a mechanism for human Lone Star virus infection?
HUMAN MODEL MISMATCH OPEN lsv_nonhuman_evidence_translation_gap
PPR:PPR1272399 contains nonhuman experimental findings but remains a 2026 preprint, so those findings are deliberately not modeled as disease mechanisms in this provisional human record. The peer-reviewed PMID:41636781 is an in vitro virus-host study and explicitly calls for further mechanistic work. Neither source independently confirms the single discordant human observation or establishes a mechanism in humans.
Show evidence (1 reference)
PMID:41636781 NO_EVIDENCE In Vitro
"Our data illustrate key distinctions from previous Bandavirus reports and underline the need for future studies to explore the mechanisms of LSV replication and pathogenesis."
The peer-reviewed in vitro report leaves LSV mechanisms unresolved and does not independently support a mechanism for human disease.

Phenotypes

1
Meningoencephalitis Neurologic HP:0002383 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Infectious encephalitis (HP:0002383). HP:0002383 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:39983710 SUPPORT Human Clinical
"We identified 2 bunyaviruses, POTV and LSV, associated with fatal cases of meningoencephalitis in immunocompromised patients."
The paper associates one of its two fatal cases with LSV. PARTIAL is used because association in a single case does not establish that LSV caused the syndrome or that it is a recurring LSV phenotype.
🦠

Infectious Agent

1
Lone Star virus
NCBI Taxonomy identifies NCBITaxon:1219465 as Lone Star virus, within the species Bandavirus amblyommae. This exact virus identity is used instead of similarly named tick-associated viruses.
Lone Star virus NCBITaxon:1219465 NCBI Taxonomy (NCBITaxon)
Show evidence (1 reference)
PMID:23637969 SUPPORT Other
"Here we sought to characterize the growth characteristics and genome of Lone Star virus (LSV), an unclassified bunyavirus originally isolated from the lone star tick Amblyomma americanum."
The peer-reviewed genome report independently identifies the named virus and its original tick source; NCBI Taxonomy remains the authority for the ontology identifier.
↔️

Transmission

1
Putative Amblyomma americanum vector association
Lone Star virus has been isolated from Amblyomma americanum, and the human case-report authors describe that tick as a putative vector. This records virus ecology only; transmission from this tick to humans has not been established.
Show evidence (2 references)
PMID:23637969 SUPPORT Other
"Here we sought to characterize the growth characteristics and genome of Lone Star virus (LSV), an unclassified bunyavirus originally isolated from the lone star tick Amblyomma americanum."
Isolation from A. americanum supports a tick association but does not by itself demonstrate a transmission route to humans.
PMID:39983710 SUPPORT Other
"Both Heartland virus and LSV use A. americanum ticks as a putative tick vector."
The source explicitly hedges the vector assignment as putative; PARTIAL preserves that uncertainty and does not imply proven human transmission.
{ }

Source YAML

click to show
name: Lone Star Virus Infection
creation_date: "2026-08-08T20:38:51Z"
category: Infectious Disease
synonyms:
- LSV infection
description: >-
  This is a provisional record for one published human observation associated
  with Lone Star virus. The report concerned an immunocompromised adult with
  fatal meningoencephalitis, but etiologic attribution remains uncertain: an
  initial cerebrospinal-fluid detection was reproduced only at the originating
  laboratory and was not reproduced by later testing at a second laboratory;
  additional confirmation was negative. The record does not define a general
  clinical spectrum, established human transmission route, diagnostic case
  definition, or established causal disease entity.
parents:
- Viral Infection
references:
- reference: PMID:39983710
  title: Two Human Cases of Fatal Meningoencephalitis Associated with Potosi and Lone Star Virus Infections, United States, 2020-2023.
- reference: PPR:PPR1272399
  title: Reverse genetics and comparative pathogenesis of Lone star virus
- reference: PMID:5810802
  title: "Arbovirus studies in the Ohio-Mississippi Basin, 1964-1967. VII. Lone Star virus, a hitherto unknown agent isolated from the tick Amblyomma americanum (Linn)."
- reference: PMID:23637969
  title: "The genome sequence of Lone Star virus, a highly divergent bunyavirus found in the Amblyomma americanum tick."
- reference: PMID:41636781
  title: Exploring the Relationship Between Lone Star Virus and Synaptogyrin-2 Using Novel Viral and Host Models of Infections.
infectious_agent:
- name: Lone Star virus
  infectious_agent_term:
    preferred_term: Lone Star virus
    term:
      id: NCBITaxon:1219465
      label: Lone Star virus
  description: >-
    NCBI Taxonomy identifies NCBITaxon:1219465 as Lone Star virus, within the
    species Bandavirus amblyommae. This exact virus identity is used instead of
    similarly named tick-associated viruses.
  evidence:
  - reference: PMID:23637969
    reference_title: "The genome sequence of Lone Star virus, a highly divergent bunyavirus found in the Amblyomma americanum tick."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Here we sought to characterize the growth characteristics and genome of
      Lone Star virus (LSV), an unclassified bunyavirus originally isolated
      from the lone star tick Amblyomma americanum.
    explanation: >-
      The peer-reviewed genome report independently identifies the named virus
      and its original tick source; NCBI Taxonomy remains the authority for the
      ontology identifier.
transmission:
- name: Putative Amblyomma americanum vector association
  description: >-
    Lone Star virus has been isolated from Amblyomma americanum, and the human
    case-report authors describe that tick as a putative vector. This records
    virus ecology only; transmission from this tick to humans has not been
    established.
  evidence:
  - reference: PMID:23637969
    reference_title: "The genome sequence of Lone Star virus, a highly divergent bunyavirus found in the Amblyomma americanum tick."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Here we sought to characterize the growth characteristics and genome of
      Lone Star virus (LSV), an unclassified bunyavirus originally isolated
      from the lone star tick Amblyomma americanum.
    explanation: >-
      Isolation from A. americanum supports a tick association but does not by
      itself demonstrate a transmission route to humans.
  - reference: PMID:39983710
    reference_title: Two Human Cases of Fatal Meningoencephalitis Associated with Potosi and Lone Star Virus Infections, United States, 2020-2023.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Both Heartland virus and LSV use A. americanum ticks as a putative tick
      vector.
    explanation: >-
      The source explicitly hedges the vector assignment as putative; PARTIAL
      preserves that uncertainty and does not imply proven human transmission.
phenotypes:
- category: Neurologic
  name: Meningoencephalitis
  description: >-
    Fatal meningoencephalitis was reported in the single human observation
    associated with Lone Star virus. The association is not modeled as proven
    causation or as an established phenotype frequency.
  phenotype_term:
    preferred_term: Infectious encephalitis
    term:
      id: HP:0002383
      label: Infectious encephalitis
  context: >-
    One immunocompromised adult; no general Lone Star virus clinical spectrum
    can be inferred from this observation.
  evidence:
  - reference: PMID:39983710
    reference_title: Two Human Cases of Fatal Meningoencephalitis Associated with Potosi and Lone Star Virus Infections, United States, 2020-2023.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We identified 2 bunyaviruses, POTV and LSV, associated with fatal cases
      of meningoencephalitis in immunocompromised patients.
    explanation: >-
      The paper associates one of its two fatal cases with LSV. PARTIAL is used
      because association in a single case does not establish that LSV caused
      the syndrome or that it is a recurring LSV phenotype.
mechanistic_hypotheses:
- hypothesis_group_id: lsv_etiologic_attribution
  hypothesis_label: Lone Star virus etiologic attribution in the reported case
  status: EMERGING
  description: >-
    Lone Star virus may have caused or contributed to the reported fatal
    meningoencephalitis, but the detection was reproduced only at the
    originating laboratory and is insufficient to establish causality; later
    testing at a second laboratory did not confirm it.
  evidence:
  - reference: PMID:39983710
    reference_title: Two Human Cases of Fatal Meningoencephalitis Associated with Potosi and Lone Star Virus Infections, United States, 2020-2023.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      CSF mNGS testing, which we performed twice on a hospital day 3 sample,
      was positive for Lone star virus (LSV).
    explanation: >-
      Records the initial observation supporting an LSV association in the
      reported case without treating it as proof of etiology.
  - reference: PMID:39983710
    reference_title: Two Human Cases of Fatal Meningoencephalitis Associated with Potosi and Lone Star Virus Infections, United States, 2020-2023.
    supports: REFUTE
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Additional testing of residual CSF by CDC did not detect reads from LSV
      on mNGS, and confirmatory testing with viral isolation and plaque
      reduction neutralization testing was negative.
    explanation: >-
      The non-reproduced result and negative additional confirmation weaken a
      definitive etiologic interpretation.
discussions:
- discussion_id: lsv_etiologic_attribution_uncertainty
  prompt: >-
    Did Lone Star virus cause the fatal meningoencephalitis in the single
    reported human observation?
  kind: INTERPRETATION
  status: OPEN
  attaches_to:
  - mechanistic_hypotheses#lsv_etiologic_attribution
  - phenotypes#Meningoencephalitis
  rationale: >-
    The initial result supports an association, but later testing at a second
    laboratory did not reproduce it and other confirmation was negative. The
    source itself cautions that molecular detection alone does not establish
    causality in a highly susceptible host. Independent human observations and
    reproducible confirmation would be needed before asserting a causal entity
    or a broader clinical spectrum.
  evidence:
  - reference: PMID:39983710
    reference_title: Two Human Cases of Fatal Meningoencephalitis Associated with Potosi and Lone Star Virus Infections, United States, 2020-2023.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Because mNGS is a molecular detection technique and positive testing
      alone is insufficient to fulfill Koch’s postulates (23), caution is
      warranted with clinical interpretation of mNGS results, especially with
      detection of a novel agent of unclear pathogenicity in highly susceptible
      immunocompromised hosts.
    explanation: >-
      The authors explicitly limit the causal interpretation of the positive
      molecular result.
  - reference: PMID:39983710
    reference_title: Two Human Cases of Fatal Meningoencephalitis Associated with Potosi and Lone Star Virus Infections, United States, 2020-2023.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Additional testing of residual CSF by CDC did not detect reads from LSV
      on mNGS, and confirmatory testing with viral isolation and plaque
      reduction neutralization testing was negative.
    explanation: Documents the unresolved discordant confirmation.
- discussion_id: lsv_nonhuman_evidence_translation_gap
  prompt: >-
    Can currently available nonhuman studies establish a mechanism for human
    Lone Star virus infection?
  kind: HUMAN_MODEL_MISMATCH
  status: OPEN
  attaches_to:
  - mechanistic_hypotheses#lsv_etiologic_attribution
  rationale: >-
    PPR:PPR1272399 contains nonhuman experimental findings but remains a 2026
    preprint, so those findings are deliberately not modeled as disease
    mechanisms in this provisional human record. The peer-reviewed
    PMID:41636781 is an in vitro virus-host study and explicitly calls for
    further mechanistic work. Neither source independently confirms the single
    discordant human observation or establishes a mechanism in humans.
  evidence:
  - reference: PMID:41636781
    reference_title: Exploring the Relationship Between Lone Star Virus and Synaptogyrin-2 Using Novel Viral and Host Models of Infections.
    supports: NO_EVIDENCE
    evidence_source: IN_VITRO
    snippet: >-
      Our data illustrate key distinctions from previous Bandavirus reports and
      underline the need for future studies to explore the mechanisms of LSV
      replication and pathogenesis.
    explanation: >-
      The peer-reviewed in vitro report leaves LSV mechanisms unresolved and
      does not independently support a mechanism for human disease.
notes: >-
  No exact MONDO term for Lone Star virus infection was found, so disease_term
  is intentionally omitted rather than bound to a broader or invented concept.
  The exact agent is NCBITaxon:1219465 (Lone Star virus). PPR:PPR1272399 is the
  bioRxiv preprint posted on 2026-07-07 that triggered issue 6521; it is included
  as bibliographic provenance but supports no structured disease mechanism or
  human phenotype, diagnosis, transmission, or causality claim in this entry.
  PMID:39983710 is the peer-reviewed report of the single LSV-associated human
  observation. PMID:5810802 and PMID:23637969 provide foundational
  bibliographic provenance for the virus and its A. americanum association.
  PMID:41636781 was assessed but does not independently support human disease
  pathophysiology. The putative vector association is curated as virus ecology,
  not as an established route of human transmission. No experimental-model
  mechanism, LSV-specific treatment, or unsupported clinical generalization is
  curated.
datasets: []
📚

References & Deep Research

References

5
Two Human Cases of Fatal Meningoencephalitis Associated with Potosi and Lone Star Virus Infections, United States, 2020-2023.
No top-level findings curated for this source.
Reverse genetics and comparative pathogenesis of Lone star virus
No top-level findings curated for this source.
Arbovirus studies in the Ohio-Mississippi Basin, 1964-1967. VII. Lone Star virus, a hitherto unknown agent isolated from the tick Amblyomma americanum (Linn).
No top-level findings curated for this source.
The genome sequence of Lone Star virus, a highly divergent bunyavirus found in the Amblyomma americanum tick.
No top-level findings curated for this source.
Exploring the Relationship Between Lone Star Virus and Synaptogyrin-2 Using Novel Viral and Host Models of Infections.
No top-level findings curated for this source.

Deep Research

1
Claude Code
Bibliographic and Ontological Evidence Review: "Lone Star Virus Infection"
claude-haiku-4-5-20251001, claude-opus-5 25 citations 2026-08-08T15:04:12.278973

Bibliographic and Ontological Evidence Review: "Lone Star Virus Infection"

Prepared: 2026-08-08 · Scope: identity, evidence base, causality language, and preprint status only. No laboratory, clinical, or experimental-model detail is reproduced.


Scope note and method

This review answers four bounded questions using primary and authority records only: NCBI Taxonomy (E-utilities + Taxonomy Browser), NCBI Nucleotide, PubMed, Europe PMC REST, ICTV, the bioRxiv API, and the publisher (CDC Emerging Infectious Diseases) record. Peer-reviewed and preprint evidence are labeled separately throughout.

Deliberately excluded, per the requested constraints: assay procedures, isolation/culture/reverse-genetics methodology, animal-model mechanisms, doses/parameters, diagnostic or therapeutic guidance, and any generalization from the single human observation. Where the underlying sources contain such material (notably the 2026 preprint), it is cited by identity only and its substance is not summarized.


1. Taxonomic and ontological identity

1.1 Current identity

The virus called "Lone Star virus" (LSV) in PMID:39983710 and PPR:PPR1272399 resolves to a single, unambiguous taxon:

Authority Identifier Name Rank
ICTV (species) Bandavirus amblyommae species
NCBI Taxonomy txid3048183 Bandavirus amblyommae species
NCBI Taxonomy txid2734426 Lone Star bandavirus no rank (child of 3048183)
NCBI Taxonomy txid1219465 Lone Star virus no rank (child of 2734426)

Full NCBI lineage (verified by efetch db=taxonomy, 2026-08-08): Viruses → Riboviria (realm, 2559587) → Orthornavirae (kingdom, 2732396) → Negarnaviricota (phylum, 2497569) → Polyploviricotina (subphylum, 2497571) → Bunyaviricetes (class, 3151693) → Hareavirales (order, 3151839) → Phenuiviridae (family, 1980418) → Bandavirus (genus, 2733256) → Bandavirus amblyommae (species, 3048183).

An ontological point that matters for curation: NCBI retains a three-node chain, not a single node. txid1219465 ("Lone Star virus") is the virus-name node; txid2734426 ("Lone Star bandavirus") is the superseded ICTV species epithet retained as an intermediate no-rank node; txid3048183 is the current species. A KB entry that binds to txid2734426 is binding to a deprecated nomenclatural form, not to a distinct organism. The NCBI Browser species page lists "Lone Star bandavirus", "Lone Star virus", and "Lone Star virus TMA1381" as alternate names under 3048183; note that the corresponding efetch XML did not render an OtherNames block, so treat the browser synonym list as display-layer metadata rather than a stable API field.

1.2 Nomenclatural history (why three names exist)

  • 1969 — first described as an unnamed new agent from Amblyomma americanum: Kokernot RH, Calisher CH, Stannard LJ, Hayes J. Am J Trop Med Hyg 1969;18(5):789–95. PMID:5810802. (Isolate collected 1966–67.)
  • 2013 — genome sequenced and placed as a highly divergent bunyavirus (then discussed in phlebovirus terms; genus Bandavirus did not yet exist): Swei A, Russell BJ, Naccache SN, et al. PLoS One 2013;8(4):e62083. PMID:23637969, DOI:10.1371/journal.pone.0062083.
  • ~2020 — ICTV establishes genus Bandavirus; species named Lone Star bandavirus (this is the origin of NCBI txid2734426).
  • 2023 — ICTV binomial renaming of Negarnaviricota species; Lone Star bandavirusBandavirus amblyommae. Documented in Kuhn JH, Abe J, Adkins S, et al., "Annual (2023) taxonomic update…", J Gen Virol 2023;104(8), DOI:10.1099/jgv.0.001864, PMID:37622664, PMCID:PMC10721048 (abstract: "Two genera and 538 species were renamed"). A Europe PMC full-text search for the exact string "Bandavirus amblyommae" returns 3 records, of which two are this paper and the 2024 annual update (PMID:40512168, DOI:10.1099/jgv.0.002077).
  • Current ICTV release: MSL41 (2025), per https://ictv.global/msl.

Verification limitation, stated explicitly: the ICTV taxon-detail page is JavaScript-rendered and did not return taxon data to a plain fetch, and the ICTV Bandavirus report chapter does not enumerate its species inline (it states only that "Nine bandaviruses are assigned to the genus Bandavirus"). ICTV species-level assignment is therefore corroborated here indirectly but consistently by three independent lines: (a) the ICTV chapter's count of nine, which matches exactly the nine species NCBI places in genus Bandavirus; (b) NCBI's ICTV-synchronized species record; and (c) the ICTV annual-update papers above. I did not read the MSL41 spreadsheet row directly.

1.3 Reference sequence identifiers

  • RefSeq (reference genome, isolate TMA 1381): NC_021242.1 (L, 6,341 bp), NC_021243.1 (M, 3,313 bp), NC_021244.1 (S, 1,876 bp).
  • Original GenBank deposits (Swei et al. 2013): KC589005.1, KC589006.1, KC589007.1.
  • Sequences derived from the human observation (see §2): PQ347830.1 (297 bp), PQ347831.1 (224 bp), PQ347832.1 (140 bp) — all partial S segment, strain UC1, /host="Homo sapiens", /isolation_source="cerebrospinal fluid", /country="USA: Idaho", /collection_date=2023, submitted 14-SEP-2024 by Chiu CY & Servellita V (UCSF), released 12-OCT-2024. These three records carry the GenBank UNVERIFIED: flag in their DEFINITION lines. That flag is part of the primary record and should be carried into any provenance annotation; it is a documented qualification on the only human-derived sequence evidence that exists for this virus.

Total NCBI Nucleotide holdings under txid1219465[Organism:exp]: 15 records (3 RefSeq + 3 GenBank originals + 3 human-derived partials + 6 associated protein/duplicate entries).

1.4 Distinguishing similarly named tick-associated entities

An exhaustive NCBI Taxonomy name search for "lone star virus" OR "lone star bandavirus" OR "lone star tick" returns exactly three taxa: 1219465, 2734426, and 6943. The following are the realistic confusion set:

Entity NCBI txid Species Family Relationship to LSV
Lone star tick (Amblyomma americanum) 6943 Amblyomma americanum Ixodidae Not a virus. The arthropod whose common name supplies the virus's name. The single most likely ontological mis-binding.
Heartland virus 1216928 Bandavirus heartlandense Phenuiviridae Congeneric, same tick species association, and an established human pathogen with its own literature. Distinct taxon; do not merge or transfer claims.
Bourbon virus 1618189 Thogotovirus bourbonense Orthomyxoviridae Different family, different order, different class. Also A. americanum-associated and an established human pathogen. Frequently co-listed with LSV in "lone star tick viruses" reviews.
Bhanja virus 1213620 Bandavirus bhanjanagarense Phenuiviridae Congeneric. Note the species epithet is bhanjanagarense, not bhanjaense — a common transcription error.
SFTS virus Bandavirus dabieense Phenuiviridae Congeneric; the genus type/most-studied member.
Potosi virus 273360 Orthobunyavirus potosiense Peribunyaviridae Not a bandavirus and not tick-associated. Critical for this review: Potosi virus is the other virus in the same publication (PMID:39983710) and concerns a different patient. Claims about the two must not be pooled.

The nine NCBI species in genus Bandavirus are: albatrossense (3051988), amblyommae (3048183), bhanjanagarense (3051989), dabieense (2748958), guertuense (3051991), heartlandense (3051992), kismaayoense (3051993), razdanense (3051994), zwieselense (3059756).

One further disambiguation trap: pre-2020 literature (including PMID:23637969) describes LSV as an unclassified/divergent "bunyavirus" or discusses it in phlebovirus terms. That is the same virus under superseded higher classification, not a separate entity.


2. Peer-reviewed human observations

2.1 Count: one

Exactly one peer-reviewed human observation associated with Bandavirus amblyommae has been published — a single patient.

Exhaustive searches performed 2026-08-08: - PubMed "lone star virus" (all fields): 5 records total — PMIDs 42384674, 41636781, 39983710, 23637969, 5810802. Of these, only 39983710 contains a human observation. - Europe PMC "lone star virus" (all sources, MED + PPR + PMC): 52 records. Manual triage of the full result set found no additional human case report, human case series, or LSV-specific human seroprevalence study. The non-LSV-specific hits are reviews, tick-virome and vector surveys, Heartland/Bourbon serosurveys in wildlife, SFTSV-focused work, and ICTV taxonomy updates. - The two other 2026 LSV-titled peer-reviewed papers are not human observations: PMID:41636781 (Eaton CW, et al., Vector Borne Zoonotic Dis 2026;26(6):355–64, DOI:10.1177/15303667261420983) concerns viral and host model systems; PMID:42384674 (Li C, et al., Virulence 2026;17(1):2696699) is a genus-level Bandavirus comparison. Their content is out of the scope constraints of this review and, being non-human, cannot be used to characterize human disease.

2.2 The single observation

Citation (peer-reviewed): Chiu CY, Godasi RR, Hughes HR, Servellita V, Foresythe K, Tubati A, Zorn K, Sidhu S, Wilson MR, Bethina SV, Abenroth D, Cheng Y, Grams R, Reese C, Isada C, Thottempudi N. "Two Human Cases of Fatal Meningoencephalitis Associated with Potosi and Lone Star Virus Infections, United States, 2020–2023." Emerging Infectious Diseases 2025;31(2):215–221. DOI:10.3201/eid3102.240831. PMID:39983710. PMCID:PMC11845157. Publication type: Case Reports; Journal Article.

What was reported for the LSV patient (Case 2 of 2): a 60-year-old man from Idaho, USA, with a history of common variable immunodeficiency, presenting with "a 1-week history of headache and myalgias" and mental-status changes, in whom cerebrospinal fluid metagenomic next-generation sequencing was "positive for Lone star virus (LSV)". The reported syndrome is fatal meningoencephalitis; the patient "died 26 days after admission."

Constraints on how this may be represented: - n = 1. This is one patient. No frequency, penetrance, incidence, case-fatality rate, or recurring clinical spectrum can be derived from it, and none is asserted here. - Case 1 of the same paper is a different virus (Potosi virus, Orthobunyavirus potosiense, Peribunyaviridae). The paper's title and abstract cover both; only Case 2 pertains to LSV. - The paper does not claim priority. It does not state that this is the first human detection of LSV, and no such claim should be attributed to it. What can be said, as a negative bibliographic finding: no earlier peer-reviewed human observation for this virus was found in PubMed or Europe PMC. - The paper's own framing is associative, not causal — "Associated with" in the title, and "associated with fatal cases of meningoencephalitis in immunocompromised patients" in the Discussion.


3. Discordant confirmation and the authors' causality language

3.1 The discordance (stated at the minimum level needed to assess causality)

Detection and confirmation did not agree between laboratories. Reported verbatim by the authors:

"Additional testing of residual CSF by CDC did not detect reads from LSV on mNGS, and confirmatory testing with viral isolation and plaque reduction neutralization testing was negative."

At the originating laboratory, detection was internally reproducible across sequencing runs (initially 50 of 14,386,666 reads aligning to the LSV genome at 84%–95% identity; a subsequent higher-depth run yielded 2,460 reads mapping to all three genome segments, covering 1,601 bp (13.6%) of the 11,730-bp trisegmented genome, with 183 SNPs and pairwise identity of 88.6%).

The authors attribute the inter-laboratory discordance to "potential sample degradation caused by multiple freeze–thaw cycles and longer storage times" and to "differences in sample preparation methods." That is their stated explanation; it is an attribution, not an independent resolution of the discordance.

Net position: the detection was sequence-based only, reproduced within one laboratory, and not independently confirmed — a second, independent laboratory failed to redetect it and returned negative results on two orthogonal confirmatory approaches. The corresponding sequence deposits are additionally flagged UNVERIFIED: by GenBank (§1.3). No supporting serologic confirmation is reported; the authors separately note that serologic testing "is problematic for highly immunocompromised patients, for whom results can be false-negative."

3.2 What the peer-reviewed authors say about causality

The authors explicitly decline a causal claim:

"Because mNGS is a molecular detection technique and positive testing alone is insufficient to fulfill Koch's postulates, caution is warranted with clinical interpretation of mNGS results, especially with detection of a novel agent of unclear pathogenicity in highly susceptible immunocompromised hosts."

and:

"Further clinical and epidemiologic studies are needed to characterize the spectrum of clinical disease and pathogenicity associated with POTV and LSV infections in humans."

Explicit statement of uncertainty. Etiologic causality is not established. The published evidence supports a claim of the form "viral RNA was detected in the CSF of one immunocompromised patient with fatal meningoencephalitis, without independent confirmation" — an association reported in a single patient. It does not support "Bandavirus amblyommae causes meningoencephalitis," "LSV is a human pathogen," or any statement about human transmission, diagnosis, treatment, phenotype frequency, or pathogenicity. The authors themselves characterize LSV as "a novel agent of unclear pathogenicity."


4. Status of PPR:PPR1272399 / DOI:10.64898/2026.07.06.736858

Field Value Source
Title "Reverse genetics and comparative pathogenesis of Lone star virus" bioRxiv API; Europe PMC
Europe PMC ID PPR1272399 (source PPR) Europe PMC REST
DOI 10.64898/2026.07.06.736858 bioRxiv API
Server bioRxiv ("server": "bioRxiv") bioRxiv API
Posted 2026-07-07 (date); Europe PMC firstPublicationDate 2026-07-07 bioRxiv API; Europe PMC
Version 1 bioRxiv API
Type / category "new results" / microbiology bioRxiv API
License CC BY-NC-ND bioRxiv API
Corresponding author Natasha Louise Tilston-Lunel bioRxiv API
Authors Omoga DCA; Witt C; Giesel H; Bowen JM; Gunter K; Pozuelos S; Relich R; Brennan B; Tilston-Lunel NL bioRxiv API
Peer-review status Preprint. Not peer reviewed.
Published journal version None. bioRxiv API "published": "NA"; Europe PMC returns no commentCorrectionList / linked published version bioRxiv API; Europe PMC

Metadata note for curation: Europe PMC renders the last author as "Tilston NL", while bioRxiv gives "Tilston-Lunel, N. L." — an indexing truncation of a hyphenated surname, not two different people. Also note the unusual DOI prefix 10.64898 (not the legacy 10.1101 bioRxiv prefix); the bioRxiv API nonetheless returns server: bioRxiv for this DOI, confirming the server assignment. Where the DOI stem encodes 2026.07.06 and the posting date is 2026-07-07, cite 2026-07-07 as the posting date.

Relationship to the human report. The preprint cites the peer-reviewed human observation as its motivation. Its abstract states that LSV "remains poorly studied, and its pathogenic potential is not well defined," and that "Recent detection of LSV RNA in cerebrospinal fluid from an immunocompromised patient in Idaho, U.S., with fatal meningoencephalitis further highlights the need" for further study. The Idaho patient is Case 2 of PMID:39983710 (§2.2) — so the two documents are linked by the preprint referencing the case report as background, not by any shared patient data, and not by any confirmation of the human finding.

The preprint is a laboratory virology study. Its experimental content — model systems, reverse-genetics work, comparative outcomes, and cross-protection findings — is outside the scope of this review by the stated constraints and is not summarized here. Two points bear on evidence weight only:

  1. It is preprint evidence, uncertified by peer review, version 1, with no journal version as of 2026-08-08.
  2. It contains no human observation and therefore cannot corroborate the Idaho detection, cannot resolve the inter-laboratory discordance in §3.1, and cannot be used to infer human pathogenicity, transmission, or clinical phenotype.

Summary of evidence tiers

Claim Strongest available support Tier
Identity = Bandavirus amblyommae, genus Bandavirus, family Phenuiviridae NCBI txid3048183; ICTV MSL41; Kuhn et al. 2023 (PMID:37622664) Authority record
Virus originally isolated from Amblyomma americanum (1969) PMID:5810802 Peer-reviewed
Reference genome (isolate TMA 1381) NC_021242–NC_021244; PMID:23637969 Authority record + peer-reviewed
One patient with fatal meningoencephalitis and CSF detection of LSV RNA PMID:39983710 (Case 2) Peer-reviewed, n=1, case report
Independent confirmation of that detection Absent — discordant; CDC mNGS, isolation, and PRNT negative Peer-reviewed negative result
Etiologic causality in that patient Not established; authors invoke Koch's postulates as unfulfilled Explicitly unresolved
LSV as a human pathogen generally No supporting evidence found; authors describe "unclear pathogenicity" Unsupported
Laboratory characterization of LSV pathogenesis PPR:PPR1272399 (bioRxiv, 2026-07-07, v1) Preprint, non-human, not peer reviewed

Verification limitations

Three things I could not verify directly and am not asserting as verified: (a) the ICTV MSL41 spreadsheet row for Bandavirus amblyommae was not read — ICTV species assignment is corroborated indirectly as described in §1.2; (b) the ICTV taxon-detail page did not render to a plain fetch, so no ICTV taxnode_id is reported; (c) full texts of PMID:41636781 and PMID:42384674 were screened by title/abstract-level metadata rather than read in full, though both are non-human by title and neither returned as a human-observation record in the Europe PMC sweep.


Sources

One operational note unrelated to the report's content: several claude.ai MCP connectors in this session (PubMed, OLS, and others) are unauthenticated and could not be used here, so all queries went through public REST/E-utilities endpoints instead. Authorizing those connectors in an interactive session would let a future run query PubMed and OLS directly.