Insights into the genetic characteristics, clustering patterns, and phylogeographic dynamics of the JC polyomavirus, 1993 to 2023.

The human JC polyomavirus (JCV) is a widespread, neurotropic, opportunistic pathogen responsible for progressive multifocal leukoencephalopathy (PML) as well as other diseases in immunosuppressed individuals, including granule cell neuronopathy, JCV-associated nephropathy, encephalitis, and meningitis in rare cases. JCV classification is still unclear, where the ICTV (International Committee on Taxonomy of Viruses) has grouped all the strains into human polyomavirus 2, with no classification on clade and subclade levels. Therefore, JCV strains were previously classified using different genomic regions, e.g., full-length, VP1, and the V-T intergenic region etc., and the strains were grouped into several types related to various geographic locations and human ethnicities. However, neither of these classifications and nomenclature contemplates all the groups described so far. Herein, we evaluated all the available full-length coding genomes, VP1, and large T antigen nucleotide sequences of JCV reported during 1993-2023 and classified them into four major phylogenetic clades, i.e., GI-GIV, where GI is further grouped into two types GI.1 and GI.2 with five sub-clades each (GI.1/GI.2 a-e), GII into three (GII a-c), GIII as a separate clade, and GIV into seven sub-clades (GIV a-g). Similarly, the phylogeographic network analysis indicated four major clusters corresponding to GI-GIV clades, each with multiple subclusters and mutational sub-branches corresponding to the subclades. GI and GIV clusters are connected via GI.1-e reported from Europe and America, GII, GIII and GIV clusters are connected by GII-b and GII-c strains reported from Africa, while GIV cluster strains are connected to the Russia-Italy JCV haplotype. Furthermore, we identified JCV-variant-GS/B-Germany-1997 (GenBank ID: AF004350.1) as an inter-genotype recombinant having major and minor parents in the GI.1-e and GII-a clades, respectively. Additionally, the amino acid variability analysis revealed high entropy across all proteins. The large T antigen exhibited the highest variability, while the small t antigen showed the lowest variability. Our phylogenetic and phylogeographic analyses provide a new approach to genotyping and sub-genotyping and present a comprehensive classification system of JCV strains based on their genetic characteristics and geographic distribution, while the genetic recombination and amino acid variability can help identify pathogenicity and develop effective preventive and control measures against JCV infections.

A molecular evaluation of dengue virus pathogenesis and its latest vaccine strategies.

More than one third of the world's population living in tropical and subtropical areas of the world is at risk of dengue infections and as many as 100 million people are yearly infected. This disease has reemerged during the past 20 years in the form of an epidemic. Dengue is caused by one of four related serotypes of dengue virus and often leads to severe forms of the disease, resulting commonly from secondary infections. Dengue virus is a mosquito borne virus, belongs to the family Flaviviridae and consists of a single stranded positive sense RNA genome. Like other RNA viruses it escapes defense mechanisms and neutralization attempts by mutations, which make it more resistant and adaptable to its environment. Antiviral strategies and vaccine development is thus impaired and hence to date there is no licensed vaccine available for dengue virus. Here we discuss various efforts made towards the identification of potential vaccine targets for dengue as well as various strategies employed by research groups/pharmaceutical companies towards the development of a successful dengue vaccine.

PCR-Based Molecular Diagnosis of Hepatitis Virus (HBV and HDV) in HCV Infected Patients and Their Biochemical Study.

Seroprevalence of HCV indicates that HCV is found in more than 10% of HBV- or HDV-infected patients worldwide leading to liver disease. Here we show HBV and HDV coinfection association with HCV infected Pakistani patients, study of disease severity, and possible interpretation of associated risk factors in coinfected patients. A total of 730 liver diseased patients were included, out of which 501 were found positive for HCV infection via PCR. 5.1% of patients were coinfected with HBV while 1% were coinfected with HBV and HDV both. LFTs were significantly altered in dually and triply infected patients as compared to single HCV infection. Mean bilirubin, AST, and ALT levels were highest (3.25 mg/dL, 174 IU/L, and 348 IU/L) in patients with triple infection while dual infection LFTs (1.6 mg/dL, 61 IU/L, and 74 IU/L) were not high as in single infection (1.9 mg/dL, 76 IU/L, and 91 IU/L). The most prominent risk factor in case of single (22%) and dual infection (27%) group was "reuse of syringes" while in triple infection it was "intravenous drug users" (60%). It is concluded that HBV and HDV coinfections are strongly associated with HCV infected Pakistani patients and in case of severe liver disease the possibility of double and triple coinfection should be kept in consideration.