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1.
Antiviral Res ; 209: 105490, 2023 01.
Article in English | MEDLINE | ID: mdl-36521633

ABSTRACT

Human infection with Sosuga virus (SOSV), a recently discovered pathogenic paramyxovirus, has been reported in one individual to date. No animal models of disease are currently available for SOSV. Here, we describe initial characterization of experimental infection in Syrian hamsters, including kinetics of virus dissemination and replication, and the corresponding clinical parameters, immunological responses, and histopathology. We demonstrate susceptibility of hamsters to infection in the absence of clinical signs or significant histopathologic findings in tissues.


Subject(s)
Paramyxoviridae , Cricetinae , Animals , Humans , Mesocricetus , Paramyxoviridae/physiology , Models, Animal , Disease Models, Animal
2.
J Infect Dis ; 223(5): 752-764, 2021 03 03.
Article in English | MEDLINE | ID: mdl-33502471

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to produce substantial morbidity and mortality. To understand the reasons for the wide-spectrum complications and severe outcomes of COVID-19, we aimed to identify cellular targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tropism and replication in various tissues. METHODS: We evaluated RNA extracted from formalin-fixed, paraffin-embedded autopsy tissues from 64 case patients (age range, 1 month to 84 years; 21 COVID-19 confirmed, 43 suspected COVID-19) by SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR). For cellular localization of SARS-CoV-2 RNA and viral characterization, we performed in situ hybridization (ISH), subgenomic RNA RT-PCR, and whole-genome sequencing. RESULTS: SARS-CoV-2 was identified by RT-PCR in 32 case patients (21 COVID-19 confirmed, 11 suspected). ISH was positive in 20 and subgenomic RNA RT-PCR was positive in 17 of 32 RT-PCR-positive case patients. SARS-CoV-2 RNA was localized by ISH in hyaline membranes, pneumocytes, and macrophages of lungs; epithelial cells of airways; and endothelial cells and vessel walls of brain stem, leptomeninges, lung, heart, liver, kidney, and pancreas. The D614G variant was detected in 9 RT-PCR-positive case patients. CONCLUSIONS: We identified cellular targets of SARS-CoV-2 tropism and replication in the lungs and airways and demonstrated its direct infection in vascular endothelium. This work provides important insights into COVID-19 pathogenesis and mechanisms of severe outcomes.


Subject(s)
COVID-19/virology , Endothelium, Vascular/virology , Respiratory System/virology , SARS-CoV-2/physiology , Virus Replication , Adolescent , Adult , Aged , Aged, 80 and over , Autopsy , COVID-19/complications , COVID-19 Nucleic Acid Testing , Child , Child, Preschool , Female , Humans , In Situ Hybridization , Infant , Lung/virology , Male , Middle Aged , RNA, Viral/isolation & purification , Real-Time Polymerase Chain Reaction , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Viral Tropism , Whole Genome Sequencing , Young Adult
3.
Emerg Infect Dis ; 23(3): 405-414, 2017 03.
Article in English | MEDLINE | ID: mdl-27959260

ABSTRACT

Zika virus is causally linked with congenital microcephaly and may be associated with pregnancy loss. However, the mechanisms of Zika virus intrauterine transmission and replication and its tropism and persistence in tissues are poorly understood. We tested tissues from 52 case-patients: 8 infants with microcephaly who died and 44 women suspected of being infected with Zika virus during pregnancy. By reverse transcription PCR, tissues from 32 (62%) case-patients (brains from 8 infants with microcephaly and placental/fetal tissues from 24 women) were positive for Zika virus. In situ hybridization localized replicative Zika virus RNA in brains of 7 infants and in placentas of 9 women who had pregnancy losses during the first or second trimester. These findings demonstrate that Zika virus replicates and persists in fetal brains and placentas, providing direct evidence of its association with microcephaly. Tissue-based reverse transcription PCR extends the time frame of Zika virus detection in congenital and pregnancy-associated infections.


Subject(s)
Abortion, Spontaneous , Brain/virology , Placenta/virology , RNA, Viral/isolation & purification , Virus Replication/physiology , Zika Virus Infection/virology , Zika Virus/isolation & purification , Adolescent , Adult , Female , Fetus/virology , Humans , Infant , Infectious Disease Transmission, Vertical , Microcephaly , Pregnancy , Pregnancy Complications, Infectious/virology , Reverse Transcriptase Polymerase Chain Reaction , Young Adult
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