SARS-CoV-2 Infects Hamster Testes

Campos, Rafael K.; Camargos, Vidyleison Neves; Azar, Sasha R.; Haines, Clint A.; Eyzaguirre, Eduardo; Rossi, Shannan L.

doi:10.3390/microorganisms9061318

Cited by 20 publications

(10 citation statements)

References 67 publications

(73 reference statements)

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“…The complex vasculature and known ACE2 expression of the tissues of the MGT make it a potential target of the virus 11,[41][42][43] . The SARS-CoV-2 infection of the testicles has been reported in mouse and hamster respiratory challenge models [44][45][46] . Likewise, the testicles are also a target of Ebola and Zika virus during systemic infection 47 .…”

Section: Discussionmentioning

confidence: 99%

An immunoPET probe to SARS-CoV-2 reveals early infection of the male genital tract in rhesus macaques

Madden

Thomas

Blair

et al. 2022

Preprint

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Because of the recognized systemic nature of SARS-CoV-2 infection, a non-invasive and unbiased method is needed to clarify its spatiotemporal dynamics in vivo after transmission. We recently developed a probe based on the anti-SARS-CoV-2 spike antibody CR3022 to study SARS-CoV-2 pathogenesis in vivo. Herein, we describe its use in immunoPET to investigate SARS-CoV-2 infection of rhesus macaques. Using PET/CT imaging of macaques at different times post-SARS-CoV-2 inoculation, we demonstrate that the 64Cu-labelled CR3022-F(ab′)2 probe targeting the spike protein of SARS-CoV-2 can be used to study the dynamics of infection within the respiratory tract and uncover novel sites of infection. Differences in lung pathology between infection with the WA1 isolate and the delta variant were readily observed using immunoPET and corroborated CT lung pathology. The ability of the probe to illuminate lung-associated pathology demonstrates its specificity and function to detect infection in PET scan. The 64Cu-CR3022-probe also demonstrated dynamic changes occurring between 1- and 2-weeks post-infection. Remarkably, a robust signal was seen in the male genital tract (MGT) of all three animals studied. Infection of the MGT was validated by immunofluorescence imaging of infected cells in the testicular and penile tissue and severe pathology was observed in the testes of one animal at 2-weeks post-infection. The results presented here underscore the utility of using immunoPET to study the dynamics of SARS-CoV-2 infection to understand its pathogenicity and discover new anatomical sites of viral replication. We provide direct evidence for SARS-CoV-2 infection of the MGT in rhesus macaques revealing the possible pathologic outcomes of viral replication at these sites.

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Section: Discussionmentioning

confidence: 99%

An immunoPET probe to SARS-CoV-2 reveals early infection of the male genital tract in rhesus macaques

Madden

Thomas

Blair

et al. 2022

Preprint

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“…This also raises questions for further investigation about the role of other sex-related hormones, particularly testosterone, as the authors noted. Also, SARS-CoV-2 has been detected in the testes of infected golden Syrian hamsters and may be important to understanding fundamental aspects of short- and long-term impact of COVID-19 in male reproductive health ( 17 ).…”

Section: Commentarymentioning

confidence: 99%

Golden Syrian Hamsters as a Model for Revisiting the Role of Biological Sex Differences in SARS-CoV-2 Infection

Michita

Mysorekar

2021

mBio

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There is growing evidence that coronavirus disease 2019 (COVID-19) affects males more severely than females, including compelling evidence indicating that biological sex is an important clinical factor influencing disease pathology and outcomes. In their recent article in mBio , Dhakal et al. find further evidence to support this hypothesis as they interrogate biological sex differences in the pathogenesis and clinical features of COVID-19 in the golden Syrian hamster model.

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“…Previous studies had already identified alterations in testicular endocrine function in 119 men of reproductive age infected with SARS-CoV-2, which had demonstrated an increase in LH levels and a decrease in the testosterone/LH ratio, probably reflecting an injury to Leydig cells, causing an early stage of transient hypogonadism (Ma et al, 2020;Drevet et al, 2021;Teixeira et al, 2021). In other reports, low testosterone levels were also identified in patients with COVID-19, but the samples showed alterations such as a reduction in Leydig cells, intense orchitis, and injury to the seminiferous tubules, which could explain the pathologic findings (Campos et al, 2021;Selvaraj et al, 2021;Duarte Neto et al, 2022). Hormonal regulation is more complex and dependent on sites and signals other than the gonads, which make up only a part of the hypothalamic-pituitary axis (Liu et al, 2018).…”

Section: Discussionmentioning

confidence: 83%

SARS-CoV-2 Nucleocapsid Protein is Associated With Lower Testosterone Levels: An Experimental Study

et al. 2022

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The ongoing COVID-19 pandemic represents an extra burden in the majority of public and private health systems worldwide beyond the most pessimistic expectations, driving an urgent rush to develop effective vaccines and effective medical treatments against the SARS-CoV-2 pandemic. The Nucleocapsid structural viral protein is remarkably immunogenic and hugely expressed during infection. High IgG antibodies against Nucleocapsid protein (N protein) levels were detected in the serum of COVID-19 patients, confirming its pivotal antigen role for a T lymphocyte response in a vaccine microenvironment. Currently, adverse events associated with immunizations have raised some degree of concern, irrespective of its huge benefits in dealing with disease severity and decreasing mortality and morbidity. This hitherto study evaluates histological changes in rats’ testes, epididymis, prostate, and seminal vesicles and analyzes hormone levels after solely N protein inoculation. Therefore, we exposed a group of Lewis rats to weekly injections of the recombinant N protein for 28 days, while a control group was inoculated with a buffer solution. The N group revealed a more significant number of spermatozoa. Spermatozoa in the seminiferous tubules were counted in twenty 400 × microscopy fields (mean of 9.2 vs. 4.6 in the control group; p < 0,01), but significantly lower testosterone levels (mean of 125.70 ng/dl vs. 309,00 ng/dl in the control group; p < 0,05) were found. No other histological and biochemical changes were displayed. Conclusively, these data suggest testicular hormonal imbalance mediated by the SARS-CoV-2 N protein that could be linked to reported post-COVID-19 syndrome hypogonadism. More relevant research might be performed to confirm this viral antigen’s deleterious mechanism in the human testicular microenvironment, particular in Leydig cell function.

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SARS-CoV-2 Infects Hamster Testes

Cited by 20 publications

References 67 publications

An immunoPET probe to SARS-CoV-2 reveals early infection of the male genital tract in rhesus macaques

An immunoPET probe to SARS-CoV-2 reveals early infection of the male genital tract in rhesus macaques

Golden Syrian Hamsters as a Model for Revisiting the Role of Biological Sex Differences in SARS-CoV-2 Infection

SARS-CoV-2 Nucleocapsid Protein is Associated With Lower Testosterone Levels: An Experimental Study

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