Transcription and Replication in the Human Polyomaviruses

2003 ◽  
pp. 73-126 ◽  
Author(s):  
Hee-Sun Kim ◽  
John W. Henson ◽  
Richard J. Frisque
Author(s):  
Maria Dolci ◽  
Lucia Signorini ◽  
Wafa Toumi ◽  
Giuseppe Basile ◽  
Sarah D'Alessandro ◽  
...  

2021 ◽  
Author(s):  
Zongsong Wu ◽  
Fabrice E Graf ◽  
Hans H Hirsch
Keyword(s):  

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1052
Author(s):  
Rameez Hassan Pirzada ◽  
Muhammad Haseeb ◽  
Maria Batool ◽  
MoonSuk Kim ◽  
Sangdun Choi

The rapid spread of the virus, the surge in the number of deaths, and the unavailability of specific SARS-CoV-2 drugs thus far necessitate the identification of drugs with anti-COVID-19 activity. SARS-CoV-2 enters the host cell and assembles a multisubunit RNA-dependent RNA polymerase (RdRp) complex of viral nonstructural proteins that plays a substantial role in the transcription and replication of the viral genome. Therefore, RdRp is among the most suitable targets in RNA viruses. Our aim was to investigate the FDA approved antiviral drugs having potential to inhibit the viral replication. The methodology adopted was virtual screening and docking of FDA-approved antiviral drugs into the RdRp protein. Top hits were selected and subjected to molecular dynamics simulations to understand the dynamics of RdRp in complex with these drugs. The antiviral activity of the drugs against SARS-CoV-2 was assessed in Vero E6 cells. Notably, both remdesivir (half-maximal effective concentration (EC50) 6.6 μM, 50% cytotoxicity concentration (CC50) > 100 µM, selectivity index (SI) = 15) and ledipasvir (EC50 34.6 μM, CC50 > 100 µM, SI > 2.9) exerted antiviral action. This study highlights the use of direct-acting antiviral drugs, alone or in combination, for better treatments of COVID-19.


Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1473
Author(s):  
Junxing Zhao ◽  
Jianming Qiu ◽  
Sadikshya Aryal ◽  
Jennifer L. Hackett ◽  
Jingxin Wang

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. The 3′ untranslated region (UTR) of this β-CoV contains essential cis-acting RNA elements for the viral genome transcription and replication. These elements include an equilibrium between an extended bulged stem-loop (BSL) and a pseudoknot. The existence of such an equilibrium is supported by reverse genetic studies and phylogenetic covariation analysis and is further proposed as a molecular switch essential for the control of the viral RNA polymerase binding. Here, we report the SARS-CoV-2 3′ UTR structures in cells that transcribe the viral UTRs harbored in a minigene plasmid and isolated infectious virions using a chemical probing technique, namely dimethyl sulfate (DMS)-mutational profiling with sequencing (MaPseq). Interestingly, the putative pseudoknotted conformation was not observed, indicating that its abundance in our systems is low in the absence of the viral nonstructural proteins (nsps). Similarly, our results also suggest that another functional cis-acting element, the three-helix junction, cannot stably form. The overall architectures of the viral 3′ UTRs in the infectious virions and the minigene-transfected cells are almost identical.


2006 ◽  
Vol 281 (42) ◽  
pp. 31348-31358 ◽  
Author(s):  
Grant A. Darnell ◽  
Wayne A. Schroder ◽  
Joy Gardner ◽  
David Harrich ◽  
Hong Yu ◽  
...  

2003 ◽  
Vol 16 (3) ◽  
pp. 269-276 ◽  
Author(s):  
V. Pietropaolo ◽  
D. Fioriti ◽  
P. Simeone ◽  
M. Videtta ◽  
C. Di Taranto ◽  
...  

The distribution of DNA of BK and JC human polyomaviruses (BKV and JCV) was investigated in samples from autopsies of different organs in 2 groups of patients: Human Immunodeficiency Virus −1 (HIV) positive and negative. Samples from various organs were analysed by a nested polymerase chain reaction (PCR) for the non-coding control and for the VP1 regions of both viruses. The results obtained showed that BKV DNA was present in both males and females with a higher prevalence in HIV-positive subject samples (spleen: 33%; kidney: 44%; brain: 22%, uterine cervix:100%; prostatic urethra: 50%). In prostatic urethra samples of HIV-positive subjects, the JCV DNA was revealed in a low percentage (33%), while it was not found at all in uterine cervix samples of both groups. The varying presence of BK and JC viral DNA in the different organs seems to reflect the different pathogenetic attitude of these viruses. JCV was mainly present in the brain (55%), confirming its typical neurotropism and its etiological role in neurological disorders found in immunodeficient patients. BKV, on the other hand, was mainly present in the kidney (44%) and in genital organs (uterine cervix: 100%; prostatic urethra: 50%) with the latter finding favouring the hypothesis of a possible sexual transmission of BKV. Furthermore, our results confirm the crucial role of the immune system in the persistence of human polyomaviruses in the host.


2004 ◽  
Vol 10 (s2) ◽  
pp. 29-29
Author(s):  
U Moens ◽  
OP Rekvig
Keyword(s):  

mSphere ◽  
2016 ◽  
Vol 1 (6) ◽  
Author(s):  
Lora H. Rigatti ◽  
Tuna Toptan ◽  
Joseph T. Newsome ◽  
Patrick S. Moore ◽  
Yuan Chang

ABSTRACT Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies. Polyomaviruses (PyVs) are known to infect a wide range of vertebrates and invertebrates and are associated with a broad spectrum of diseases, including cancers, particularly in immune-suppressed hosts. A novel polyomavirus, designated rat polyomavirus 2 (RatPyV2), was identified from a breeding colony of rats having X-linked severe combined immunodeficiency. Using a human panpolyomavirus immunohistochemistry test (P-PIT), RatPyV2 was initially detected in the parotid salivary gland of a colony member. Rolling circle amplification using DNA from harderian and parotid glands identified a novel 5.1-kb polyomavirus genome closely related to human Washington University (WU) and Karolinska Institute (KI) and vole polyomaviruses but notably divergent from Rattus norvegicus PyV1 (RnorPyV1; also designated RatPyV1). Further screening showed RatPyV2 inclusion body infection in the lung epithelium and variably in other respiratory, reproductive, and glandular tissues of 12/12 (100%) rats. IMPORTANCE Although P-PIT was developed to detect diseases associated with known human polyomaviruses, the identification of a new polyomavirus in rats suggests that it may have utility as a broad-based screen for new, as well as known polyomaviruses. Our findings suggest that RatPyV2 may be a commensal infection of laboratory rats that can lead to disseminated disease in T cell immune-deficient rats. Infection of the X-SCID rats with RatPyV2 and Pneumocystis carinii is a potential model for coinfection pathogenesis and treatment options during transplant preclinical studies.


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