Yellow Fever Virus DNA in Urine and Semen of Convalescent Patient, Brazil

Barbosa, Célia Marisa Rizzatti; Paola, Nicholas Di; Cunha, Marielton dos Passos; Rodrigues-Jesus, Mônica Josiane; Araújo, Danielle Bastos; Silveira, Vanessa Barbosa da; Leal, Fabyano Bruno; Mesquita, Fernando Silveira; Botosso, Viviane Fongaro; Zanotto, Paolo M. A.; Durigon, Edison L.; Silva, Marcos; Oliveira, Danielle Bruna Leal

doi:10.3201/eid2401.171310

Cited by 48 publications

(57 citation statements)

References 10 publications

(9 reference statements)

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“…We observed extrahepatic lesions that undoubtedly contributed to the worsening of patients’ clinical conditions, with YFV‐Ag and YFV‐RNA detectable in organs other than the liver. Detection of YFV‐RNA by qRT–PCR in the kidneys and in two testis samples casts light on the recent description of YFV‐RNA detected up to 21 days after the onset of symptoms in the semen and urine of a YF patient . These findings may indicate the genitourinary tract as a persistent reservoir of YFV, allowing infection of a hepatic graft or even causing late hepatitis, which may occur during disease convalescence …”

Section: Discussionmentioning

confidence: 95%

“…Detection of YFV-RNA by qRT-PCR in the kidneys and in two testis samples casts light on the recent description of YFV-RNA detected up to 21 days after the onset of symptoms in the semen and urine of a YF patient. 26 These findings may indicate the genitourinary tract as a persistent reservoir of YFV, allowing infection of a hepatic graft or even causing late hepatitis, which may occur during disease convalescence. 16 The finding of pancreatitis, not previously emphasised in YF, was remarkable in the present series, with clinical symptoms before OLT (patients had abdominal pain and elevated amylase/lipase).…”

Section: Discussionmentioning

confidence: 96%

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Yellow fever and orthotopic liver transplantation: new insights from the autopsy room for an old but re‐emerging disease

et al. 2019

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Aims The clinical spectrum of yellow fever (YF) ranges from asymptomatic to fulminant hepatitis. During the sylvatic YF epidemic in the metropolitan area of São Paulo, Brazil in 2018, seven orthotopic liver transplantations (OLTs) were performed in our institution to treat fulminant YF hepatitis. Three patients recovered, while four patients died following OLT. The autopsy findings of all these cases are presented herein as the first description of YF in transplanted patients. Methods and results All patients were men, aged 16–40 years, without vaccination to YF virus (YFV). All organs were examined, with tissue sampling for histopathological analysis. Detection of YF virus antigens (YFV Ag) was performed with two primary antibodies (mouse polyclonal anti‐YFV antibody directed to wild strain and a goat anti‐YF virus antibody), and RT–PCR assays were utilised to detect YFV‐RNA. All the cases depicted typical findings of YF hepatitis in the engrafted liver. The main extrahepatic findings were cerebral oedema, pulmonary haemorrhage, pneumonia, acute tubular necrosis and ischaemic/reperfusion pancreatitis. Of the four cases, the YVF Ag was detected in the heart in one case, liver and testis in three cases, and the kidney and spleen in all four cases. All four cases had YF virus RNA detected by RT–PCR in the liver and in other organs. Conclusions Infection of the engrafted liver and other organs by YFV, possibly combined with major ischaemic systemic lesions, may have led to the death of four of the seven patients undergoing OLT.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 96%

Yellow fever and orthotopic liver transplantation: new insights from the autopsy room for an old but re‐emerging disease

et al. 2019

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“…Mosquito-vectored flaviviruses that can result in persistent infections are usually associated with an accumulation of adaptive mutations, suggesting that viral genetics may also play an important role for establishing persistence. Examples of mutations in viruses causing persistence were shown with ZIKV, WNV [78][79][80], JEV [81], YFV [24,82], and DENV [23]. These mutations happen in different viral proteins and appear to affect various viral functions, but in general attenuate the virus to cause less cytopathic effects, which is likely important for persistence.…”

Section: Viral Genetic Changes Associated With Persistencementioning

confidence: 99%

“…West Nile virus (WNV) was proposed to have been possibly sexually transmitted in a clinical study of a woman who developed meningo-encephalitis by WNV 2 weeks after intercourse with an infected individual [22]. Other medically important flaviviruses, dengue virus (DENV) [23] and yellow fever virus (YFV) [24], have both been detected in human semen. DENV RNA was detected in a man returning from Thailand to Italy at 37 days post onset of symptoms, when virus RNA was not detectable in the serum or urine anymore [23].…”

Section: Introductionmentioning

confidence: 99%

“…Detection of DENV RNA in the seminal fluid is nevertheless not commonly reported, and another study that performed PCR in the semen of five man with acute DENV infection failed to detect any viral RNA [25]. YFV RNA was detected in urine and semen, but not in the serum, and the virus was isolated from urine on day 21 post onset the symptoms [24]. Another flavivirus, Japanese encephalitis virus (JEV), can be naturally found in porcine semen [26].…”

Section: Introductionmentioning

confidence: 99%

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Animal Models of Zika Virus Sexual Transmission

Campos¹,

McDonald²,

Brault³

et al. 2021

Current Concepts in Zika Research

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ZIKV was first identified in the 1940s as a mosquito-borne virus; however, sexual transmission, which is uncommon for arboviruses, was demonstrated more than 60 years later. Tissue culture and animal models have allowed scientists to study how this transmission is possible. Immunocompromised mice infected with ZIKV had high viral loads in their testes, and infection of immunocompetent female mice was achieved following intravaginal inoculation or inoculation via mating with an infected male. These mouse studies lead researchers to investigate the individual components of the male reproductive system. In cell culture and mouse models, ZIKV can persist in Sertoli and germ cells of the testes and epithelial cells in the epididymis, which may lead to sexual transmission even after ZIKV has been cleared from other tissues. ZIKV has also been studied in nonhuman primates (NHPs), which appears to mimic the limited human epidemiological data, with low rates of symptomatic individuals and similar clinical signs. Although refinement is needed, these animal models have proven to be key in ZIKV research and continue to help uncovering the mechanisms of sexual transmission. This review will focus on the animal models used to elucidate the mechanisms of sexual transmission and persistence of flaviviruses.

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Urine is a viral antigen reservoir in hepatitis E virus infection

Dong

Tian

et al. 2023

Hepatology

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Background and Aims: HEV ORF2 antigen (Ag) in serum has become a tool for diagnosing current HEV infection. Particularly, urinary shedding of HEV Ag has been gaining increasing interest. We aim to uncover the origin, antigenicity, diagnostic performance, and diagnostic significance of Ag in urine in HEV infection.Approach and Results: Clinical serum and urine samples from patients with acute and chronic HEV infection were analyzed for their Ag levels. Ag in urine was analyzed by biochemical and proteomic approaches. The origin of urinary Ag and Ag kinetics during HEV infection was investigated in mouse and rabbit models, respectively. We found that both the Ag level and diagnostic sensitivity in urine were higher than in serum. Antigenic protein in urine was an E2slike dimer spanning amino acids 453-606. pORF2 entered urine from serum in mice i.v. injected with pORF2. Ag in urine originated from the secreted form of pORF2 (ORF2 S ) that abundantly existed in hepatitis E patients' serum. HEV Ag was specifically taken up by renal cells and was disposed into urine, during which the level of Ag was concentrated >10-fold, resulting in the higher diagnosing sensitivity of urine Ag than serum Ag. Moreover, Ag in urine appeared 6 days earlier, lasted longer than viremia and antigenemia, and showed good concordance with fecal RNA in a rabbit model.

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Yellow Fever Virus DNA in Urine and Semen of Convalescent Patient, Brazil

Cited by 48 publications

References 10 publications

Yellow fever and orthotopic liver transplantation: new insights from the autopsy room for an old but re‐emerging disease

Yellow fever and orthotopic liver transplantation: new insights from the autopsy room for an old but re‐emerging disease

Animal Models of Zika Virus Sexual Transmission

Urine is a viral antigen reservoir in hepatitis E virus infection

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