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Pre-exposure prophylaxis (PrEP) strategies utilizing anti-retroviral drugs show considerable promise for HIV prevention. However there is insufficient pharmacokinetic (PK) data on drug concentrations required for protection at the relevant mucosal tissues where the infection is initiated. Here we evaluated the utility of a humanized mouse model to derive PK data on two leading drugs, the RT inhibitor...
Live-attenuated influenza virus (LAIV) prime-boost vaccination previously conferred protection against heterologous H3N2 swine influenza challenge, including in piglets with maternally derived antibodies (MDA). Conversely, a whole-inactivated virus (WIV) vaccine was associated with enhanced disease. This study was aimed at identifying immune correlates of cross-protection. Piglets with and without...
The major burden of influenza morbidity resides within the elderly population. The challenge managing influenza-associated illness in the elderly is the decline of immune function, where mechanisms leading to immunological senescence have not been elucidated. To better represent the immune environment, we investigated clinical morbidity and immune function during sequential homologous and heterologous...
Novel flaviviruses that are genetically related to pathogenic mosquito-borne flaviviruses (MBFV) have been isolated from mosquitoes in various geographical locations, including Finland. We isolated and characterized another novel virus of this group from Finnish mosquitoes collected in 2007, designated as Ilomantsi virus (ILOV). Unlike the MBFV that infect both vertebrates and mosquitoes, the MBFV-related...
The nonstructural protein 9 (Nsp9) of porcine reproductive and respiratory syndrome virus (PRRSV) is a RNA-dependent RNA polymerase (RdRp) that plays a vital role in viral replication. This study first demonstrated that the Nsp9 of genotype 2 PRRSV interacted with cellular retinoblastoma protein (pRb), and Nsp9 co-localized with pRb in the cytoplasm of PRRSV-infected MARC-145 cells and pulmonary alveolar...
The role of cellular proteases and endosome maturation in the entry of caliciviruses including porcine enteric calicivirus (PEC), murine norovirus (MNV)-1 and feline calicivirus (FCV) were investigated. Treatment with chloroquine or cathepsin L inhibitors, but not cathepsin B inhibitors, significantly reduced the replication of PEC, MNV and FCV. When concentrated PEC, MNV or FCV were incubated with...
The mechanism of amiloride inhibition of Coxsackievirus B3 (CVB3) and poliovirus type 1 (PV1) RNA replication was investigated using membrane-associated RNA replication complexes. Amiloride was shown to inhibit viral RNA replication and VPgpUpU synthesis. However, the drug had no effect on polymerase elongation activity during either (−) strand or (+) strand synthesis. These findings indicated that...
To deepen our understanding of early rectal transmission of HIV-1, we studied virus–host interactions in the rectal mucosa using simian immunodeficiency virus (SIV)-Indian rhesus macaque model and mRNA deep sequencing. We found that rectal mucosa actively responded to SIV as early as 3 days post-rectal inoculation (dpi) and mobilized more robust responses at 6 and 10dpi. Our results suggest that the...
Molecular epidemiologic studies of North American (NA) West Nile virus (WNV; Flaviviridae, Flavivirus) have documented the displacement of the introduced NY99 genotype with WN02. In addition, these studies have shown that particular substitutions are under positive selection. One occurs in the C-terminus of the NS4A coding sequence and results in a valine to methionine substitution at position nine...
Chikungunya virus (CHIKV) causes an acute clinical illness characterized by sudden high fever, intense joint pain, and skin rash. Recent outbreaks of chikungunya disease in Africa and Asia are a major public health concern; however, there is currently no effective licensed vaccine or specific treatment. This study reported the development of a mouse monoclonal antibody (MAb), CK47, which recognizes...
Cellular receptors for KSHV attachment and entry were characterized using tyramide signal amplification (TSA)-enhanced confocal microscopy. Integrins αVβ3, αVβ5 and α3β1 were detected on essentially all the actin-based cell surface microdomains that initially bind KSHV, while the presence of CD98 and heparan sulfate (HS), the putative attachment receptor, was more variable. KSHV bound to the same...
The oncoprotein Tax of human T-cell leukemia virus type 1 (HTLV-1) is a potent transactivator of viral and cellular transcription. Here, we identified ELL2 as the sole transcription elongation factor to be specifically upregulated in HTLV-1-/Tax-transformed T-cells. Tax contributes to regulation of ELL2, since transient transfection of Tax increases ELL2 mRNA, Tax transactivates the ELL2 promoter,...
A novel mycovirus tentatively assigned the name Sclerotinia sclerotiorum hypovirus 2 (SsHV2/5472) was detected in the phytopathogenic fungus Sclerotinia sclerotiorum. The genome is 14581 nucleotides (nts) long, excluding the poly (A) tail. A papain-like cysteine protease (Pro), an RNA-dependent RNA polymerase (RdRp) and a helicase (Hel) domain were detected in the polyprotein. Phylogenetic analysis...
Having a history of infection with one pathogen may sometimes provide a level of T cell-dependent protective heterologous immunity to another pathogen. This immunity was initially thought due to cross-reactive T cell epitopes, but recent work has suggested that such protective immunity can be initiated nonspecifically by the action of cytokines on memory T cells. We retested this concept using two...
Enterovirus 71 (EV71) infection can induce encephalitis. Overt immune responses is suspected to cause severe symptoms, so anti-inflammatory agents, corticosteroids have been recommended for treatment. However, one clinical study reported that treatment with glucocorticoids, dexamethasone (Dex) exacerbates disease severity. Here we investigated Dex treatment on EV71 infection using the murine model...
Human enterovirus 71 (EV71) belongs to the genus Enterovirus in the family Picornaviridae and has been recognized as one of the most important pathogens that cause emerging infectious disease. Despite of the importance of EV71, the nonstructural protein 3AB from this virus is little understood for its function during EV71 replication. Here we expressed EV71 3AB protein as recombinant protein in a...
Due to climate change and the propagation of competent arthropods worldwide, arboviruses have become pathogens of major medical importance. Early transmission to vertebrates is initiated by skin puncture and deposition of virus together with arthropod saliva in the epidermis and dermis. Saliva components have the capacity to modulate skin cell responses by enhancing and/or counteracting initial replication...
Paramyxoviruses contain a bi-lipidic envelope decorated by two transmembrane glycoproteins and carpeted on the inner surface with a layer of matrix proteins (M), thought to bridge the glycoproteins with the viral nucleocapsids. To characterize M structure-function features, a set of M domains were mutated or deleted. The genes encoding these modified M were incorporated into recombinant Sendai viruses...
Although the production of single gene knockout viruses is a useful strategy to study viral gene functions, the redundancy of many host interactive genes within a complex viral genome can obscure their collective functions. In this study, a rabbit-specific poxvirus, myxoma virus (MYXV), was genetically altered to disrupt multiple members of the poxviral ankyrin-repeat (ANK-R) protein superfamily,...
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