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Viral capsid proteins (CPs) are characterized by their role in forming protective shells around viral genomes. However, CPs have additional and important roles in the virus infection cycles and in the cellular responses to infection. These activities involve CP binding to RNAs in both sequence-specific and nonspecific manners as well as association with other proteins. This review focuses on CPs of...
To study the membrane orientation of flavivirus non-structural proteins (NSPs) in the replication complex, the seven major West Nile (WN) NSPs were separately expressed in monkey cells, and their subcellular localization was investigated by imaging-based techniques. First, we observed by confocal microscopy that four small transmembrane proteins (TP) (NS2A, NS2B, NS4A, and NS4B) were located to the...
Inhibition of cellular respiration, oxidation of glutathione and induction of apoptosis have been reported in epithelial cells infected in vitro with influenza A virus (IAV). Here, the same biomarkers were investigated in vivo by assessing the lungs of BALB/c mice infected with IAV. Cellular respiration declined on day 3 and recovered on day 7 post-infection. For days 3–5, the rate (mean±SD) of respiration...
Erythrovirus B19 (B19V) is a member of the family Parvoviridae. Infection with B19V has been linked to a variety of diseases including erythroid, thyroid, neurological and autoimmune diseases. Here we show that infection of primary CD36+ cells with B19V coincides with downregulation of thyroid, retinoid, and estrogen hormone receptors. In addition we show changes in expression of a variety of related...
Human influenza viruses predominantly bind α2,6 linked sialic acid (SA) while avian viruses bind α2,3 SA-containing complex glycans. Virulence and tissue tropism of influenza viruses have been ascribed to this binding preference. We generated 2009 pandemic H1N1 (pH1N1) viruses with either predominant α2,3 or α2,6 SA binding and evaluated these viruses in mice and ferrets. The α2,3 pH1N1 virus had...
Since the liver drains antigens from the intestinal tract, and since the intestinal tract is a major site of viral replication, we examined the dynamics of liver macrophages (Kupffer cells) throughout SIV infection. Absolute numbers of Kupffer cells increased in the livers in acute infection, and in animals with AIDS. Significantly higher percentages of proliferating (BrdU+) Kupffer cells were detected...
Nipah virus (NiV) is a recently emerged severe human pathogen that belongs to the Henipavirus genus within the Paramyxoviridae family. The NiV genome is encapsidated by the nucleoprotein (N) within a helical nucleocapsid that is the substrate used by the polymerase for transcription and replication. The polymerase is recruited onto the nucleocapsid via its cofactor, the phosphoprotein (P). The NiV...
The ecological model, Daphnia pulex (Cladocera: Daphniidae), is broadly distributed in Holarctic freshwater habitats and has been the subject of multidisciplinary study for over half a century, but never has a natural RNA virus infection been reported in daphnids. Here we report on a group of paleoviruses related to RNA dependent RNA polymerase in the genome of D. pulex. Phylogenetic analysis suggests...
The rodent parvoviruses are known to be oncoselective, and lytically infect many transformed human cells. Because current therapeutic regimens for metastatic melanoma have low response rates and have little effect on improving survival, this disease is a prime candidate for novel approaches to therapy, including oncolytic parvoviruses. Screening of low-passage, patient-derived melanoma cell lines...
Bacteriophage ATP-based packaging motors translocate DNA into a pre-formed prohead through a dodecameric portal ring channel to high density. We investigated portal–terminase docking interactions at specifically localized residues within a terminase-interaction region (aa279–316) in the phage T4 portal protein gp20 equated to the clip domain of the SPP1 portal crystal structure by 3D modeling. Within...
HIV latency constitutes the main barrier for clearing HIV infection from patients. Our inability to recognize and isolate latently infected cells hinders the study of latent HIV. We engineered two HIV-based viral reporters expressing different fluorescent markers: one HIV promoter-dependent marker for productive HIV infection, and a second marker under a constitutive promoter independent of HIV promoter...
We are investigating canine distemper virus (CDV) as a vaccine vector for the delivery of HIV envelope (Env) that closely resembles the native trimeric spike. We selected CDV because it will promote vaccine delivery to lymphoid tissues, and because human exposure is infrequent, reducing potential effects of pre-existing immunity. Using SIV Env as a model, we tested a number of vector and gene insert...
The Soybean mosaic virus (SMV) coat protein (CP) is necessary for virion assembly and viral cell-to-cell and long-distance movements in plants. We previously showed that the C-terminal region of the SMV CP is required for CP self-interaction. In the present study, we generated SMV mutants containing CPs with single amino acid substitutions of the charged amino acids in the C-proximal region. Infectivity...
Covalent conjugation of immune-stimulatory compounds to protein antigens is a potential means to self-adjuvant non-replicating subunit vaccines. Previously, it was demonstrated that covalent coupling of a Toll-like receptor (TLR) ligand to the exterior HIV-1 envelope glycoprotein, gp120, enhanced its immunogenicity. However, the consequences of chemical conjugation to gp120 on broadly neutralizing...
We examined the ability of HIV-1 subtype C to develop resistance to the inhibitory lectins, griffithsin (GRFT), cyanovirin-N (CV-N) and scytovirin (SVN), which bind multiple mannose-rich glycans on gp120. Four primary HIV-1 strains cultured under escalating concentrations of these lectins became increasingly resistant tolerating 2 to 12 times their 50% inhibitory concentrations. Sequence analysis...
The Gyrovirus genus consists of the immunosuppressive Chicken Anemia Virus (CAV) prototype and since 2011 three other viral species found in sera/tissues of chickens, human feces, and on human skin. Here the genomes of two other gyrovirus species were characterized in diarrhea samples from Tunisian children whose main ORFs shared amino acid identity of 46–59% with those of the previously characterized...
Biomotors have been classified into linear and rotational motors. For 35 years, it has been popularly believed that viral dsDNA-packaging apparatuses are pentameric rotation motors. Recently, a third class of hexameric motor has been found in bacteriophage phi29 that utilizes a mechanism of revolution without rotation, friction, coiling, or torque. This review addresses how packaging motors control...
Pigs are considered to be “mixing vessels” for the emergence of influenza viruses with pandemic potential. 2009 Pandemic Influenza H1N1 further proved this hypothesis, and raised the needs for risk assessment of human cases caused by swine influenza virus.A field investigation was conducted after a case identified with infection of European avian-like swine influenza H1N1 virus. The diagnosis was...
Regulated processing of nepovirus polyproteins allows the release of mature proteins and intermediate polyproteins. Infectious cDNA clones of the mild NW isolate of arabis mosaic virus (ArMV) and chimeric clones incorporating RNA1 segments of Lv, a severe isolate, were generated. Clones containing the Lv X2–NTB cleavage site were not infectious unless the Lv protease was present. The Lv and NW X2–NTB...
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