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恒河猴中的SIV/SARS-CoV-2合并感染会影响病毒脱落、宿主免疫、微生物群和病毒进化。

SIV/SARS-CoV-2 coinfection in rhesus macaques impacts viral shedding, host immunity, the microbiome, and viral evolution.

作者信息

Fredericks Megan N, Kolodner Zohar, Waalkes Adam, Sawatzki Kaitlin, Hao Linhui, Long Dustin R, Penewit Kelsi, Midkiff Cecily C, McCormick Carter J, Beraki Semira, Edlefsen Paul T, Barrow Jeana, Greninger Alexander L, Gale Michael, Blair Robert V, Salipante Stephen J, Fuller Deborah H, O'Connor Megan A

机构信息

Department of Microbiology, University of Washington, Seattle, WA, United States.

Washington National Primate Research Center, Seattle, WA, United States.

出版信息

Front Immunol. 2025 May 20;16:1587688. doi: 10.3389/fimmu.2025.1587688. eCollection 2025.

DOI:10.3389/fimmu.2025.1587688
PMID:40463375
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12129928/
Abstract

People living with HIV (PLWH) have an increased risk of severe COVID-19, including prolonged viral shedding and emergence of mutations. To investigate the simian immunodeficiency virus (SIV) macaque model for HIV/SARS-CoV-2 coinfection, seven SIV+ rhesus macaques were co-infected with SARS-CoV-2. COVID-19 in all macaques was mild. SARS-CoV-2 replication persisted in the upper, but not the lower respiratory tract for 14 days post-infection. Animals showed impaired generation of anti-SARS-CoV-2 antibodies and T-cells. Animals also displayed transient changes in microbial communities in the upper airway and gastrointestinal tract. Evidence of SARS-CoV-2 evolution was observed in the upper respiratory tract. This study demonstrates that SIV/SARS-CoV-2 coinfection in rhesus macaques recapitulates aspects of COVID-19 in PLWH. We show that SIV impairs anti-SARS-CoV-2 immunity, potentially leading to prolonged viral shedding, altered pathogenesis, and viral evolution. This highlights the importance of HIV status in COVID-19 and supports the use of this model for HIV/SARS-CoV-2 coinfection.

摘要

感染人类免疫缺陷病毒（HIV）的人（PLWH）患重症2019冠状病毒病（COVID-19）的风险增加，包括病毒持续脱落和出现突变。为了研究用于HIV/SARS-CoV-2合并感染的猴免疫缺陷病毒（SIV）猕猴模型，七只感染SIV的恒河猴被SARS-CoV-2合并感染。所有猕猴的COVID-19病情均较轻。感染后14天内，SARS-CoV-2在上呼吸道而非下呼吸道持续复制。动物体内抗SARS-CoV-2抗体和T细胞的生成受损。动物的上呼吸道和胃肠道微生物群落也出现了短暂变化。在上呼吸道观察到了SARS-CoV-2进化的证据。这项研究表明，恒河猴中的SIV/SARS-CoV-2合并感染概括了PLWH中COVID-19的一些方面。我们发现SIV会损害抗SARS-CoV-2免疫力，可能导致病毒持续脱落、发病机制改变和病毒进化。这突出了HIV状态在COVID-19中的重要性，并支持将该模型用于HIV/SARS-CoV-2合并感染的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad4c/12129928/7dcf58864f82/fimmu-16-1587688-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad4c/12129928/4f04db6f24d3/fimmu-16-1587688-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad4c/12129928/c76cc0007a7f/fimmu-16-1587688-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad4c/12129928/5a489fce3335/fimmu-16-1587688-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad4c/12129928/59d2f5663cfb/fimmu-16-1587688-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad4c/12129928/2a227ecccbbd/fimmu-16-1587688-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad4c/12129928/7dcf58864f82/fimmu-16-1587688-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad4c/12129928/4f04db6f24d3/fimmu-16-1587688-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad4c/12129928/c76cc0007a7f/fimmu-16-1587688-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad4c/12129928/5a489fce3335/fimmu-16-1587688-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad4c/12129928/59d2f5663cfb/fimmu-16-1587688-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad4c/12129928/2a227ecccbbd/fimmu-16-1587688-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad4c/12129928/7dcf58864f82/fimmu-16-1587688-g006.jpg

相似文献

[1]
SIV/SARS-CoV-2 coinfection in rhesus macaques impacts viral shedding, host immunity, the microbiome, and viral evolution.

Front Immunol. 2025-5-20

[2]
SIV/SARS-CoV-2 co-infection in rhesus macaques impacts viral shedding, host immunity, the microbiome, and viral evolution.

Res Sq. 2025-3-26

[3]
Respiratory microbiome alterations, coinfections and virus intra-host evolution in a persistently active SARS-CoV-2 infection.

BMC Infect Dis. 2025-7-21

[4]
The Impact of SIV-Induced Immunodeficiency on SARS-CoV-2 Disease, Viral Dynamics, and Antiviral Immune Response in a Nonhuman Primate Model of Coinfection.

Viruses. 2024-7-21

[5]
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Infect Immun. 2023-5-16

[6]
Virological Aspects of COVID-19 in Patients with Hematological Malignancies: Duration of Viral Shedding and Genetic Analysis.

Viruses. 2024-12-31

[7]
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Cochrane Database Syst Rev. 2022-11-17

[8]
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Viruses. 2025-2-17

[9]
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Microbiol Spectr. 2022-2-23

[10]
Epigenetic modulation of the NLRP6 inflammasome sensor as a therapeutic modality to reduce necroptosis-driven gastrointestinal mucosal dysfunction in HIV/SIV infection.

Cell Commun Signal. 2025-4-25

本文引用的文献

[1]
SARS-CoV-2 infection perturbs the gastrointestinal tract and induces modest microbial translocation across the intestinal barrier.

J Virol. 2024-10-22

[2]
Non-human primate model of long-COVID identifies immune associates of hyperglycemia.

Nat Commun. 2024-8-20

[3]
The Impact of SIV-Induced Immunodeficiency on SARS-CoV-2 Disease, Viral Dynamics, and Antiviral Immune Response in a Nonhuman Primate Model of Coinfection.

Viruses. 2024-7-21

[4]
Correlates of Breakthrough SARS-CoV-2 Infections in People with HIV: Results from the CIHR CTN 328 Study.

Vaccines (Basel). 2024-4-23

[5]
T-Cell Responses to COVID-19 Vaccines and Breakthrough Infection in People Living with HIV Receiving Antiretroviral Therapy.

Viruses. 2024-4-24

[6]
Immunological and microbial shifts in the aging rhesus macaque lung during nontuberculous mycobacterial infection.

mBio. 2024-6-12

[7]
Multigroup analysis of compositions of microbiomes with covariate adjustments and repeated measures.

Nat Methods. 2024-1

[8]
The immune response to SARS-CoV-2 in people with HIV.

Cell Mol Immunol. 2024-2

[9]
Risk of COVID-19 in-hospital mortality in people living with HIV compared to general population according to age and CD4 strata: data from the ICONA network.

Int J Infect Dis. 2023-11

[10]
SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC).

Nat Immunol. 2023-10

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