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At least 19 recordsLinked to original sources

Decoding sequence recognition code of nucleic acid-binding proteins of human-infecting DNA viruses.

Human-infecting DNA viruses remain major health threats, yet the DNA-recognition mechanisms of their nucleic acid-binding proteins (NBPs) are poorly understood. Here, we systematically profiled 103 viral NBPs from human-infecting DNA viruses, with three NBPs from non-human-infecting DNA viruses as controls, using high-throughput screening. This analysis identified diverse DNA-binding motifs and specificity modules, including convergent recognition of a conserved CCACC motif across phylogenetically distant viruses. Notably, viral NBP binding-site distributions varied with genome size, and several NBPs from small-genome viruses showed enrichment on mitochondrial DNA. Functional assays further supported their mitochondrial association and effects on mitochondrial membrane potential. By integrating an ivTRT-based ssDNA-SELEX workflow, we further found that ssDNA viral NBPs recognize dimer-like and inverted-repeat sequences with potential to form stem-loop structures. Collectively, this study constructs a comprehensive viral NBP DNA-recognition atlas, offering a fundamental resource for elucidating viral genome recognition mechanisms, virus-mitochondria interactions, and developing future antiviral strategies.

Letter↗

Mechanisms of DNA virus infection: entry and early events.

The cellular components engaged in entry of viruses has been an area of intense investigation in recent years. We examine the entry and receptors used for well-studied and prevalent human DNA viruses adenoviruses, poxviruses and two herpesviruses- herpes simplex virus and Epstein-Barr virus. Little is yet known about the entry or early events for other human DNA viruses. Common themes that emerge for entry of these prevalent human DNA viruses include engagement of multiple receptors, use of cell surface molecules that are prominent and, in most cases, conserved on cells, and interactions with proteins that can alter morphology of the cytoskeleton or modulate intracellular signaling for gene expression. Where available, we provide evidence that entry not only transports the capsid and genome across a cell membrane, but that these events also can set up the cell for subsequent events that contribute to successful viral replication.

Adenoviridae↗

Ionic Contra-Viral Therapy (ICVT); a new approach to the treatment of DNA virus infections.

The sequestration of cellular K(+) has been shown elsewhere to elicit a broad spectrum of antiviral activity. The obligatory, coupled cotransports of Na(+), K(+) and Cl(-) (NKCC1) and of Na(+) and K(+) (NKATPase) effect net cellular K(+) influx. We examined the effects of specific inhibitors of these transports; a cardiac glycoside (Digoxin) and a loop diuretic (Furosemide) on virus replication in vitro. The replication of the DNA viruses, herpes simplex virus, varicella zoster virus, human cytomegalovirus and adenovirus was inhibited. There was normal replication of the RNA virus encephalomyocarditis virus. Antiviral activities of both drugs were influenced by extracellular K(+). Antiviral effects were most potent when Digoxin and Furosemide were used in combination. Targeting the host cell in this way is fundamentally different to other antiviral drug developments to date and we propose the descriptive term Ionic Contra Viral Therapy (ICVT) for the purpose of definition. We believe that specific inhibitors of coupled K(+) transports merit controlled clinical trial for a broad spectrum of DNA virus infections by local application.

Antiviral Agents↗

Role of cidofovir in the treatment of DNA virus infections, other than CMV infections, in immunocompromised patients.

Cidofovir is a nucleotide analog marketed for the treatment of human cytomegalovirus infections in immunocompromised patients. An increasing number of reports have appeared on the use of cidofovir for the treatment of other severe DNA virus infections in immunocompromised patients. The activity of cidofovir against herpes simplex viruses resistant to classic (acyclovir and/or foscavir) therapy has been widely documented. Cidofovir has also been used for the treatment of other herpesvirus infections, such as drug-resistant varicella-zoster virus, and Epstein-Barr virus-induced proliferative diseases. For papillomavirus infections, cidofovir represents a valuable alternative to the conventional therapies, which are mostly based on surgery, as in the treatment of laryngeal papillomatosis. The role of cidofovir in the treatment of polyomavirus infections is more controversial, but here too, cidofovir represents, to date, the only available efficacious therapeutic modality. Cidofovir has demonstrated activity against all poxviruses and represents a unique therapeutic modality for use against these viruses, particularly in the immunosuppressed host, should this prove necessary (eg, in a bioterrorism scenario).

Cidofovir↗

Vaccines against persistent DNA virus infections.

Persistent viruses present some particular problems for vaccine design. As for acute non-persistent viruses, the prime goal of a vaccine should be to prevent primary infection. Vaccines might also be used to modify the course of established persistent virus infections - so-called postinfective immunisation. This chapter deals with selected persistent DNA viruses, in particular the human herpes viruses.

Chickenpox↗

The effects of a DNA virus infection on the reproductive potential of female tsetse flies, Glossina morsitans centralis and Glossina morsitans morsitans (Diptera: Glossinidae).

Reproductive anomalies associated with the tsetse DNA virus infection in the female tsetse hosts, Glossina morsitans centralis Machado and Glossina morsitans morsitans Westwood, inoculated with the virus during the 3rd instar larval stage were studied and the data compared to those obtained from the control females injected with sterile physiological saline. Virus infected flies had significantly longer first and second pregnancy cycles (P < 0.0001) and produced pupae that were of significantly less weight in milligrams (P < 0.0001) compared to controls. Transmission of the virus to progeny was not absolute and only 21% of G. m. centralis and 48% of G. m. morsitans first progeny flies from infected females developed salivary gland hypertrophy as a result of transmission from mother to progeny. The virus infected females produced significantly fewere pupae compared to the controls during the experimental period (P < 0.00001).

Animals↗

Comparison of two DNA viruses infecting the marine brown algae Ectocarpus siliculosus and E. fasciculatus.

The marine brown algal genus Ectocarpus contains two species, E. siliculosus and E. fasciculatus. Field populations of both species include plants with infection symptoms caused by DNA viruses. We have established clonal cultures from infected and normal host plants and investigated the properties of the endogenous viruses. Both host species contain virus particles with a hexagonal cross-section and a diameter of ca. 150 nm. The genomes of both virus types consist of double-stranded DNA, approximately 320 kb in size. Restriction digestion with Sfil revealed differences between the two virus genomes. However, PCR experiments suggest that at least one gene, which encodes a major capsid protein, is quite similar in both virus species. In cross-infection experiments the E. siliculosus virus did not initiate an infection cycle in E. fasciculatus. In contrast, the E. fasciculatus virus infected E. siliculosus zoospores. The resulting plants showed aberrant symptoms and produced virus particles which were not infectious. We conclude that the two Ectocarpus species are hosts for different, but closely related viruses.

Capsid↗

The osmium ammine-SO2 staining method for studying the in situ configuration of viral genomes in ultrathin sections of DNA virus infected cells.

The Feulgen-like osmium ammine-SO2 method developed by Cogliati and Gautier (CR Acad Sci Ser D 1973, 276, 3041-3044) stains the DNA at the ultrastructural level. Compared to several other techniques for detecting DNA, this method remains the only one revealing the configuration of the DNA molecules within the cell whatever their compactness. In the present article we summarize the results we obtained with the osmium ammine method in the study of the fate of viral genomes along the infectious cycles in several DNA virus infected cells including adenovirus, herpes simplex virus, simian virus 40 and poxvirus. The results are discussed in relation to the replicative and transcribing activities of viral DNA.

Adenoviridae Infections↗

The effects of a tsetse DNA virus infection on the functions of the male accessory reproductive gland in the host fly Glossina morsitans centralis (Diptera; Glossinidae).

Freshly deposited third instar Glossina morsitans centralis larvae were infected with the tsetse DNA virus by microinjection, and at emergence adult males were separated from the females and fed on rabbit blood every second day for 8 days. A control group treated with sterile saline were handled similarly. They were dissected, and comparative observations made on the appearance and size of the accessory reproductive glands (ARG) in infected and control males. Regularly fed 8-day-old males from infected and control groups were mated to 2-day-old normal females obtained from the insectay. After separation from copula, the females were dissected and the uteri examined for the presence and quality of the spermatophore. The spermathecae were also examined for insemination. ARG tissues from the control and virus infected regularly fed 8-day-old male flies were fixed and processed for electron microscopic studies. The ARGs from control flies were found to be milky in appearance, whereas those from virus-infected flies were transparent in most parts. The ARGs from virus-infected males were significantly smaller in diameters (F = 42.26, p < 0.0001) and shorter (F = 200.4, p < 0. 0001) than those of the controls. Most of the virus-infected males failed to form a complete spermatophore, whereas almost all the controls formed complete spermatophore as observed in the uteri of the female mates (Chi2 = 111.661, p < 0.0001). The infected males that formed partial spermatophores and those that did not form any at all failed to inseminate their female mates. Histological studies of the ARGs revealed some lesions in the epithelial cells characterized by degeneration of cytoplasmic organelles and detachment of the muscle layer from the basal plasma membrane. However, no virus particles were observed in the affected cells.

Animals↗

The relationship between incorporation of E-5-(2-Bromovinyl)-2'-deoxyuridine into herpes simplex virus type 1 DNA with virus infectivity and DNA integrity.

E-5-(2-Bromovinyl)-2'-deoxyuridine (BrvdUrd) produced a dose-dependent shift in the density of herpes simplex virus type 1 (HSV-1) DNA at concentrations which yielded potent inhibition of virus replication in cultured Vero cells. Although the density of cellular DNA was not altered by these concentrations of BrvdUrd, incorporation of this analogue into cellular DNA of HSV-1-infected cells has been previously observed in this laboratory. The degree of inhibition correlated with the amount of BrvdUrd substituted for thymidine in HSV-1 DNA. BrvdUrd-substituted DNA was more labile as determined by a dose-dependent increase in single strand breaks when examined by centrifugation in alkaline sucrose gradients. Thus, the potent antiviral action of BrvdUrd observed in cell culture correlates not only with its incorporation into HSV-1 DNA but also with an altered stability of this DNA.

Bromodeoxyuridine↗

DNA vaccination against respiratory influenza virus infection.

DNA vaccination using plasmid encoding the hemagglutinin (HA) gene of influenza A/PR/8/34 virus to induce long-lasting protective immunity against respiratory infection was evaluated in this study. Using liposomes as carriers, the efficacy of DNA vaccines was determined using a lethal influenza infection model in mice. Mice immunized intranasally or intramuscularly with liposome-encapsulated pCI plasmid encoding HA (pCI-HA10) were completely protected against an intranasal 5 LD(50) influenza virus challenge. Mice immunized with liposome-encapsulated pCI-HA10, but not naked pCI-HA10, by intranasal administration were found to produce high titers of serum IgA. These results suggest DNA vaccines encapsulated in liposomes are efficacious in inducing complete protective immunity against respiratory influenza virus infection.

Administration, Intranasal↗

Infectivity of recombinant strawberry vein banding virus DNA.

Infectivity of the cloned DNA genome of strawberry vein banding virus (SVBV) was demonstrated by particle bombardment of 4-week-old strawberry (Fragaria vesca L. var. UC-5) plants with gold particles coated with the putative full-length 7.9 kb viral DNA. Vein banding symptoms developed on 15 % of inoculated plants 6-7 weeks post-inoculation. An approximate 1.25-mer of the viral DNA was cloned into the binary vector pCGN1547. Particle bombardment of this construct into strawberry plants gave an infection rate of 75 %. The construct was used for transformation of Agrobacterium tumefaciens, and infiltration of these cells into healthy strawberry leaves resulted in development of vein banding symptoms in 100 % of inoculated plants. Gel electrophoresis, Southern blot hybridization with an SVBV probe and sequence analyses of PCR-amplified DNA fragments were used to confirm SVBV infection in symptomatic plants.

Agrobacterium tumefaciens↗

A case-control study on a novel DNA virus (TT virus) infection and hepatocellular carcinoma. The Brescia HCC Study.

We performed a case-control study to evaluate the association of a new human DNA virus named TT virus (TTV) with hepatocellular carcinoma (HCC). We recruited 174 subjects hospitalized for HCC (84% males; mean age: 64 years) and 118 patients hospitalized for non-liver diseases in Brescia, northern Italy, as controls (94% males; mean age: 66 years). TTV DNA was found in serum by polymerase chain reaction (PCR) in 26 cases (15%) and 11 controls (9.3%) (P >. 1). TTV group 2 infection was identified in 16 cases (61.5%) and 4 controls (36.4%) (P >.1) using a type-specific PCR method. Sequence analysis of 222 nt of TTV DNA demonstrated that the remaining 10 cases and 7 controls were all infected by group 1. The odds ratio (OR) for TTV-DNA positivity, adjusted for demographic variables, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) RNA, and heavy alcohol intake was 1.8 (95% CI: 0.7-4.8; P >.1). The OR did not change when the analysis was restricted to 14 HCC cases and 56 controls who were negative for each known risk factor for HCC (OR = 1.7; 95% CI: 0.8-4.0). TTV-DNA positivity was not associated with transfusion history. The prevalence of TTV DNA was higher among HCC cases positive for HBsAg (10 of 38 [26.3%]) than among those positive for HCV RNA (8 of 62 [12.9%]) or negative for hepatitis B virus (HBV), HCV, and hepatitis G virus (HGV) infections (5 of 62 [8. 1%]) (P =.02). This study does not support the hypothesis of an association between TTV infection and HCC.

Adult↗

DNA immunization confers protection against lethal lymphocytic choriomeningitis virus infection.

DNA vaccination has been evaluated with the lymphocytic choriomeningitis virus (LCMV) model system. Plasmid DNA encoding the LCMV nucleoprotein, when injected intramuscularly, induces both antiviral antibodies and cytotoxic T lymphocytes. Injection of DNA encoding the nucleoprotein or the viral glycoprotein confers protection against normally lethal LCMV challenge in a major histocompatibility complex-dependent manner. The protection conferred is incomplete, but it is most probably mediated by the induced cytotoxic T lymphocytes.

Animals↗