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Research article · 2026 · Full text

International Journal of Biology Sciences

Molecular characterization and antiviral susceptibility profiling of Macacine alphaherpesvirus 1 isolates from captive macaques in Seoul

Kim Jae-won

Volume 8(4) · Pages 264–267 · DOI: 10.33545/26649926.2026.v8.i4c.963 ↗

Research areasHerpesvirus Infections and TreatmentsAnimal Virus Infections StudiesCytomegalovirus and herpesvirus research

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Abstract

Author-written

Approximately 80 to 90 percent of captive macaques harbor latent Macacine alphaherpesvirus 1 (McHV-1), yet molecular characterization of circulating strains in Asian primate facilities remains limited. This research characterized McHV-1 isolates from captive macaques at three facilities in Seoul, South Korea, and evaluated antiviral susceptibility profiles. Oropharyngeal and genital swabs were collected from 128 rhesus and 94 cynomolgus macaques between March and November 2024. PCR targeting glycoprotein B and DNA polymerase genes was used for detection, followed by phylogenetic analysis and plaque reduction assays against acyclovir, ganciclovir, and cidofovir. The overall PCR positivity rate was 31.5% (70/222), with rhesus macaques showing higher detection (37.5%) than cynomolgus macaques (23.4%). Phylogenetic analysis classified isolates into three genetic clades, with Clade A predominating (52.9%). Viral load correlated positively with clinical severity (r = 0.74, p < 0.001). Clade C isolates exhibited markedly elevated IC50 values for all three antivirals, suggesting reduced susceptibility. These findings provide molecular epidemiological data for McHV-1 surveillance in East Asian primate facilities and highlight the importance of strain-specific antiviral resistance profiling.

Summary

Source-checked

Plain-language reading of the full paper, prepared with AI and checked against the text. Each point links to the authors' own words.

  1. Why it matters

    • Macacine alphaherpesvirus 1 (McHV-1) is one of the most common viral agents in global primate research facilities, with 80% to 90% of captive adult macaques carrying the latent virus. View evidence ↗

      Why it matters

      Macacine alphaherpesvirus 1 (McHV-1) is one of the most common viral agents in global primate research facilities, with 80% to 90% of captive adult macaques carrying the latent virus.

      In the paper's own words

      “Approximately 80 to 90 percent of adult macaques maintained in captive breeding colonies harbor latent Macacine alphaherpesvirus 1 (McHV-1), formerly designated Cercopithecine herpesvirus 1, rendering this pathogen one of the most prevalent viral agents in primate research facilities globally”

      Page 1

      Found in: Introduction

      Read it in the full textOpen PDF at page 1 ↗
    • McHV-1 is a major concern for occupational health and animal management because it can cause fatal encephalomyelitis in humans if transmitted zoonotically. View evidence ↗

      Why it matters

      McHV-1 is a major concern for occupational health and animal management because it can cause fatal encephalomyelitis in humans if transmitted zoonotically.

      In the paper's own words

      “This high prevalence, coupled with the capacity of the virus to cause fatal encephalomyelitis upon zoonotic transmission to humans, positions McHV-1 as a pathogen of paramount concern from both animal management and occupational health perspectives”

      Page 1

      Found in: Introduction

      Read it in the full textOpen PDF at page 1 ↗
    • There is a significant knowledge gap regarding the genetic diversity of McHV-1 in Asian primate colonies, as most existing data come from North American and European facilities. View evidence ↗

      Why it matters

      There is a significant knowledge gap regarding the genetic diversity of McHV-1 in Asian primate colonies, as most existing data come from North American and European facilities.

      In the paper's own words

      “The majority of available genomic and phylogenetic data have been derived from isolates obtained in North American and European facilities, creating a substantial knowledge gap regarding the genetic diversity and evolutionary dynamics of the virus in Asian primate colonies”

      Page 1

      Found in: Introduction

      Read it in the full textOpen PDF at page 1 ↗
  2. The question

    • The study aimed to characterize McHV-1 isolates from captive macaques in Seoul using PCR and phylogenetic analysis, and to test the antiviral susceptibility of the resulting genetic clades. View evidence ↗

      The question

      The study aimed to characterize McHV-1 isolates from captive macaques in Seoul using PCR and phylogenetic analysis, and to test the antiviral susceptibility of the resulting genetic clades.

      In the paper's own words

      “The present research was conducted to characterize McHV-1 isolates from captive macaques at primate facilities in Seoul through PCR-based detection and phylogenetic analysis, and to evaluate in vitro antiviral susceptibility profiles of identified genetic clades”

      Page 1

      Found in: Introduction

      Read it in the full textOpen PDF at page 1 ↗
  3. What they did

    • A cross-sectional survey was performed between March and November 2024 at three Seoul facilities, involving 128 rhesus and 94 cynomolgus macaques. View evidence ↗

      What they did

      A cross-sectional survey was performed between March and November 2024 at three Seoul facilities, involving 128 rhesus and 94 cynomolgus macaques.

      In the paper's own words

      “A cross-sectional molecular survey was conducted from March to November 2024 at three primate holding facilities in Seoul, South Korea, encompassing 128 rhesus macaques and 94 cynomolgus macaques.”

      Page 2

      Found in: Methods

      Read it in the full textOpen PDF at page 2 ↗
    • The study used nested PCR to target a 622-bp glycoprotein B (gB) gene fragment and a 478-bp DNA polymerase (DPOL) gene fragment for detection. View evidence ↗

      What they did

      The study used nested PCR to target a 622-bp glycoprotein B (gB) gene fragment and a 478-bp DNA polymerase (DPOL) gene fragment for detection.

      In the paper's own words

      “DNA extraction was performed using the QIAamp DNA Mini Kit, followed by nested PCR amplification targeting a 622-base pair gB gene fragment and a 478-base pair DPOL gene fragment”

      Page 2

      Found in: Methods

      Read it in the full textOpen PDF at page 2 ↗
    • Antiviral susceptibility was measured using plaque reduction assays in Vero cells to determine the IC50 values for cidofovir, ganciclovir, and acyclovir. View evidence ↗

      What they did

      Antiviral susceptibility was measured using plaque reduction assays in Vero cells to determine the IC50 values for cidofovir, ganciclovir, and acyclovir.

      In the paper's own words

      “For antiviral susceptibility testing, representative isolates from each clade were propagated in Vero cells, and plaque reduction assays determined IC50 values for acyclovir, ganciclovir, and cidofovir.”

      Page 2

      Found in: Materials

      Read it in the full textOpen PDF at page 2 ↗
  4. What they found

    • Out of 222 macaques tested, 31.5% (70 animals) were positive for McHV-1 DNA. View evidence ↗

      What they found

      Out of 222 macaques tested, 31.5% (70 animals) were positive for McHV-1 DNA.

      In the paper's own words

      “Of the 222 macaques examined, 70 (31.5%) yielded positive PCR results for McHV-1 DNA in at least one specimen type.”

      Page 2

      Found in: Introduction

      Read it in the full textOpen PDF at page 2 ↗
    • Rhesus macaques had a significantly higher McHV-1 detection rate (37.5%) than cynomolgus macaques (23.4%). View evidence ↗

      What they found

      Rhesus macaques had a significantly higher McHV-1 detection rate (37.5%) than cynomolgus macaques (23.4%).

      In the paper's own words

      “Rhesus macaques demonstrated a significantly higher detection rate (48/128, 37.5%) compared to cynomolgus macaques (22/94, 23.4%; chi-square = 5.12, p = 0.024).”

      Page 2

      Found in: Discussion

      Read it in the full textOpen PDF at page 2 ↗
    • The 70 positive isolates were divided into three clades: Clade A (52.9%), Clade B (30.0%), and Clade C (17.1%). View evidence ↗

      What they found

      The 70 positive isolates were divided into three clades: Clade A (52.9%), Clade B (30.0%), and Clade C (17.1%).

      In the paper's own words

      “Phylogenetic analysis of the 70 positive isolates classified them into three distinct genetic clades. Clade A was the most prevalent, comprising 37 isolates (52.9%), followed by Clade B with 21 isolates (30.0%) and Clade C with 12 isolates (17.1%).”

      Page 2

      Found in: Introduction

      Read it in the full textOpen PDF at page 2 ↗
    • There was a significant positive correlation (r = 0.74, p < 0.001) between the viral load and the clinical severity scores of the macaques. View evidence ↗

      What they found

      There was a significant positive correlation (r = 0.74, p < 0.001) between the viral load and the clinical severity scores of the macaques.

      In the paper's own words

      “Viral load, quantified by real-time PCR, demonstrated a significant positive correlation with clinical severity scores (Pearson r = 0.74, p < 0.001)”

      Page 2

      Found in: Introduction

      Read it in the full textOpen PDF at page 2 ↗
    • Clade C isolates showed reduced susceptibility to antivirals, with higher IC50 values for acyclovir (5.1 μM), ganciclovir (3.2 μM), and cidofovir (1.7 μM) than Clades A and B. View evidence ↗

      What they found

      Clade C isolates showed reduced susceptibility to antivirals, with higher IC50 values for acyclovir (5.1 μM), ganciclovir (3.2 μM), and cidofovir (1.7 μM) than Clades A and B.

      In the paper's own words

      “Clade C isolates exhibited substantially higher IC50 values for acyclovir (5.1 μM), ganciclovir (3.2 μM), and cidofovir (1.7 μM) compared to Clades A and B”

      Page 2

      Found in: Discussion

      Read it in the full textOpen PDF at page 2 ↗
  5. What it means

    • Because Clade C is less sensitive to the first-line drug acyclovir, the authors suggest that facilities with these strains should consider alternative or combination antiviral treatments for post-exposure prophylaxis. View evidence ↗

      What it means

      Because Clade C is less sensitive to the first-line drug acyclovir, the authors suggest that facilities with these strains should consider alternative or combination antiviral treatments for post-exposure prophylaxis.

      In the paper's own words

      “The finding that Clade C isolates demonstrate reduced sensitivity to acyclovir, the first-line agent recommended for post-exposure prophylaxis, suggests that facilities housing macaques carrying Clade C strains may benefit from consideration of alternative or combination antiviral regimens.”

      Page 3

      Found in: Clinical implications

      Read it in the full textOpen PDF at page 3 ↗
    • The authors note that further research is needed to characterize the mutations causing Clade C resistance, determine if clade distribution is stable over time, and see if in vitro results translate to in vivo outcomes. View evidence ↗

      What it means

      The authors note that further research is needed to characterize the mutations causing Clade C resistance, determine if clade distribution is stable over time, and see if in vitro results translate to in vivo outcomes.

      In the paper's own words

      “Open questions include the functional characterization of mutations driving Clade C resistance, the stability of clade distribution over time, and the generalizability of these susceptibility profiles to in vivo treatment outcomes.”

      Page 3

      Found in: Discussion

      Read it in the full textOpen PDF at page 3 ↗

Visual summary

3 visuals

Illustrations explain the paper; charts are replotted from the paper's own table values.

AI-generated illustration
AI-generated conceptual illustration (Macacine alphaherpesvirus 1 particles). It explains the idea and does not show study data.↗ Enlarge
Genetic Clades and Drug Sensitivity
AI-generated conceptual illustration (Macacine alphaherpesvirus 1 particles). It explains the idea and does not show study data.

AI-generated conceptual illustration (Macacine alphaherpesvirus 1 particles). It explains the idea and does not show study data.

Open full-size image ↗

Genetic Clades and Drug Sensitivity

AI-generated conceptual illustration (Macacine alphaherpesvirus 1 particles). It explains the idea and does not show study data.

View source evidence ↗
Replotted from source data
Replotted from Table 1 (page 2) of the original paper. Every bar is the paper's own table value.↗ Enlarge
Pre-Treatment (Mean±SD) and Post-Treatment (Mean±SD): Clade A (n=37) vs Clade B (n=21) vs Clade C (n=12)
Replotted from Table 1 (page 2) of the original paper. Every bar is the paper's own table value.

Replotted from Table 1 (page 2) of the original paper. Every bar is the paper's own table value.

Open full-size image ↗

Pre-Treatment (Mean±SD) and Post-Treatment (Mean±SD): Clade A (n=37) vs Clade B (n=21) vs Clade C (n=12)

Replotted from Table 1 (page 2) of the original paper. Every bar is the paper's own table value.

View source evidence ↗
Replotted from source data
Replotted from Table 2 (page 2) of the original paper. Every bar is the paper's own table value.↗ Enlarge
PCR positivity (%): Rhesus (n=128) vs Cynomolgus (n=94)
Replotted from Table 2 (page 2) of the original paper. Every bar is the paper's own table value.

Replotted from Table 2 (page 2) of the original paper. Every bar is the paper's own table value.

Open full-size image ↗

PCR positivity (%): Rhesus (n=128) vs Cynomolgus (n=94)

Replotted from Table 2 (page 2) of the original paper. Every bar is the paper's own table value.

View source evidence ↗

Figures & tables

From the original paper
Viral load (log₁₀ copies/mL) before and after 14-dayTable 1Page 2Summary statistics of molecular characterization resultsTable 2Page 2Correlation between viral load and clinical severity scoreFigure 1Page 2Monthly viral shedding rate (%) of McHV-1 among captiveFigure 2Page 2In vitro antiviral IC₅₀ values (μM) for acyclovir, ganciclovir,Figure 3Page 3
FULL TEXT Original article · reflowed for reading

Introduction

Approximately 80 to 90 percent of adult macaques maintained in captive breeding colonies harbor latent Macacine alphaherpesvirus 1 (McHV-1), formerly designated Cercopithecine herpesvirus 1, rendering this pathogen one of the most prevalent viral agents in primate research facilities globally [1,2] . This high prevalence, coupled with the capacity of the virus to cause fatal encephalomyelitis upon zoonotic transmission to humans, positions McHV-1 as a pathogen of paramount concern from both animal management and occupational health perspectives [3] . The virus establishes lifelong latency in trigeminal and sacral ganglia of infected macaques, with periodic reactivation events resulting in oral and genital mucosal shedding that constitutes the primary source of zoonotic transmission risk [4,5] . Despite the well-documented clinical significance of McHV-1, the molecular epidemiology of circulating strains in captive primate populations across East Asia remains insufficiently characterized [6,7] . The majority of available genomic and phylogenetic data have been derived from isolates obtained in North American and European facilities, creating a substantial knowledge gap regarding the genetic diversity and evolutionary dynamics of the virus in Asian primate colonies [8] . This gap is particularly concerning given that South Korea maintains multiple primate research facilities housing both rhesus and cynomolgus macaques for biomedical experimentation, and the country represents a major hub for primate-based pharmaceutical research [9,10] . The present research was conducted to characterize McHV-1 isolates from captive macaques at primate facilities in Seoul through PCR-based detection and phylogenetic analysis, and to evaluate in vitro antiviral susceptibility profiles of identified genetic clades [11,12,13] . The outcomes are intended to inform biosafety protocols and antiviral management strategies for the regional context [14,15,16,17] .

Materials and Methods

Materials and Methods

Materials

The materials employed in this research included viral transport media for specimen collection, DNA extraction kits (QIAamp DNA Mini Kit, Qiagen, Hilden, Germany), PCR reagents including primers targeting the glycoprotein B (gB) and DNA polymerase (DPOL) genes of McHV-1, Vero cell lines for virus isolation and plaque reduction assays, antiviral agents (acyclovir, ganciclovir, and cidofovir; Sigma-Aldrich, St. Louis, MO), and molecular biology grade reagents for gel electrophoresis and sequencing preparation.

Methods

A cross-sectional molecular survey was conducted from March to November 2024 at three primate holding facilities in Seoul, South Korea, encompassing 128 rhesus macaques and 94 cynomolgus macaques. Oropharyngeal and genital swab specimens were collected under chemical sedation and stored at negative eighty degrees Celsius. DNA extraction was performed using the QIAamp DNA Mini Kit, followed by nested PCR amplification targeting a 622-base pair gB gene fragment and a 478-base pair DPOL gene fragment [7] . Positive samples were sequenced bidirectionally, and phylogenetic analysis was performed using MEGA version 11 with maximum likelihood and 1000 bootstrap replicates.

Biosafety protocols

All laboratory procedures involving McHV-1 isolates were performed within biosafety level 2 enhanced (BSL-2+) containment facilities equipped with certified Class II biological safety cabinets. Personnel conducting virus isolation and antiviral susceptibility assays utilized full personal protective equipment including double gloving, face shields, and disposable gowns. Decontamination of work surfaces was performed using 10% sodium hypochlorite solution following each experimental session. Sharps disposal protocols specific to herpesviruscontaminated materials were strictly enforced throughout the research period.

Clinical implications

The identification of clade-dependent antiviral susceptibility variation carries direct implications for the clinical management of human exposure incidents at primate facilities. The finding that Clade C isolates demonstrate reduced sensitivity to acyclovir, the first-line agent recommended for post-exposure prophylaxis, suggests that facilities housing macaques carrying Clade C strains may benefit from consideration of alternative or combination antiviral regimens. Routine molecular typing of resident McHV-1 strains could enable facility-specific tailoring of post-exposure management protocols.

Discussion

This research provides the first comprehensive molecular characterization and antiviral susceptibility profiling of McHV-1 isolates from captive macaques in South Korea.

The overall PCR detection rate of 31.5% and the classification of isolates into three phylogenetically distinct clades expand the current understanding of McHV-1 molecular epidemiology in East Asian primate populations [1, 2] .

The observed detection rate aligns with estimates from comparable captive macaque populations. Eberle and Jones-Engel [4,6] documented shedding rates of 25-35% in breeding colonies, while Favoretto et al. [10] reported 28.7% in a Brazilian facility. The higher detection in rhesus compared to cynomolgus macaques is consistent with known species-level differences in shedding dynamics [4,14] . However, in contrast to investigations reporting homogeneous McHV-1 populations within individual facilities [7] , the present research identified three cocirculating clades, likely reflecting the diverse geographic origins of procured macaques [8,15] . The reduced antiviral susceptibility in Clade C isolates likely involves polymorphisms in viral thymidine kinase or DNA polymerase genes [12,13] . From a broader perspective, these findings underscore the importance of integrating molecular surveillance with antiviral susceptibility monitoring, as the assumption of uniform sensitivity underlying current prophylaxis guidelines may require reassessment [3,9,17,18] .

Conclusion

Conclusion

Acknowledgement

AcknowledgementsThe authors acknowledge Seoul Metropolitan University for providing institutional support, laboratory infrastructure, and access to primate facilities essential for the conduct of this research. The authors recognize the contributions of the veterinary and animal care teams at the participating facilities who assisted with specimen collection, as well as the laboratory technicians who performed the molecular and virological assays. This research was supported by a grant from the National Research Foundation of Kore.

Figures and tables from the paper

Table 1. Viral load (log₁₀ copies/mL) before and after 14-day
Viral load (log₁₀ copies/mL) before and after 14-day↗ Enlarge
Table 1
Viral load (log₁₀ copies/mL) before and after 14-day

Viral load (log₁₀ copies/mL) before and after 14-day

Open full-size image ↗
Original paper figureSource PDF · page 2 ↗
Table 2. Summary statistics of molecular characterization results
ParameterRhesus (n=128)Cynomolgus (n=94)MeanRangep- value
PCR positivity (%)37.523.431.523.4- 37.50.024
Viral load (log₁₀)5.91±1.085.24±0.975.683.12- 7.840.018
Dual-site positive (%)24.513.621.413.6- 24.50.041
Severity score (mean)4.7±2.13.8±1.94.41.0-9.20.037

Table text extracted from the original PDF; superscript letters are shown inline. The original table image is below.

View original table image
Summary statistics of molecular characterization results↗ Enlarge
Table 2
Summary statistics of molecular characterization results

Summary statistics of molecular characterization results

Open full-size image ↗
Original paper tableSource PDF · page 2 ↗
Figure 1. Correlation between viral load and clinical severity score
Correlation between viral load and clinical severity score↗ Enlarge
Figure 1
Correlation between viral load and clinical severity score

Correlation between viral load and clinical severity score

Open full-size image ↗
Original paper figureSource PDF · page 2 ↗
Figure 2. Monthly viral shedding rate (%) of McHV-1 among captive
Monthly viral shedding rate (%) of McHV-1 among captive↗ Enlarge
Figure 2
Monthly viral shedding rate (%) of McHV-1 among captive

Monthly viral shedding rate (%) of McHV-1 among captive

Open full-size image ↗
Original paper figureSource PDF · page 2 ↗
Figure 3. In vitro antiviral IC₅₀ values (μM) for acyclovir, ganciclovir,
In vitro antiviral IC₅₀ values (μM) for acyclovir, ganciclovir,↗ Enlarge
Figure 3
In vitro antiviral IC₅₀ values (μM) for acyclovir, ganciclovir,

In vitro antiviral IC₅₀ values (μM) for acyclovir, ganciclovir,

Open full-size image ↗
Original paper figureSource PDF · page 3 ↗

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  18. Nakamura T, Yamashita K, Fujimoto S, Tanaka H. Phylogenomic analysis of Macacine alphaherpesvirus 1 diversity in Asian macaque populations. Arch Virol. 2025;170(1):45-58.