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At least 19 recordsLinked to original sources
PubMed2004

RNA interference acts as a natural antiviral response to O'nyong-nyong virus (Alphavirus; Togaviridae) infection of Anopheles gambiae.

RNA interference (RNAi) is triggered in eukaryotic organisms by double-stranded RNA (dsRNA), and it destroys any mRNA that has sequence identity with the dsRNA trigger. The RNAi pathway in Anopheles gambiae can be silenced by transfecting cells with dsRNA derived from exon sequence of the A. gambiae Argonaute2 (AgAgo2) gene. We hypothesized that RNAi may also act as an antagonist to alphavirus replication in A. gambiae because RNA viruses form dsRNA during replication. Silencing AgAgo2 expression would make A. gambiae mosquitoes more permissive to virus infection. To determine whether RNAi conditions the vector competence of A. gambiae for O'nyong-nyong virus (ONNV), we engineered a genetically modified ONNV that expresses enhanced GFP (eGFP) as a marker. After intrathoracic injection, ONNV-eGFP slowly spread to other A. gambiae tissues over a 9-day incubation period. Mosquitoes were then coinjected with virus and either control beta-galactosidase dsRNA (dsbetagal; note that "ds" is used as a prefix to indicate the dsRNA derived from a given gene throughout) or ONNV dsnsP3. Treatment with dsnsP3 inhibited virus spread significantly, as determined by eGFP expression patterns. ONNV-eGFP titers from mosquitoes coinjected with dsnsP3 were significantly lower at 3 and 6 days after injection than in mosquitoes coinjected with dsbetagal. Mosquitoes were then coinjected with ONNV-eGFP and dsAgAgo2. Mosquitoes coinjected with virus and AgAgo2 dsRNA displayed widespread eGFP expression and virus titers 16-fold higher than dsbetagal controls after 3 or 6 days after injection. These observations provide direct evidence that RNAi is an antagonist of ONNV replication in A. gambiae, and they suggest that the innate immune response conditions vector competence.

Alphavirus↗
PubMed1981

Ross River virus (Togaviridae: Alphavirus) infection (epidemic polyarthritis) in American Samoa.

An outbreak of Ross River virus infection (epidemic polyarthritis), which occurred in American Samoa between August 1979 and January 1980, is described. On the basis of a serological survey performed near the end of the epidemic, it is estimated that at least 13,500 people were infected. Ross River virus was isolated from the blood of a single polyarthritis patient. Plaque reduction neutralization tests, using this virus strain, were done on 393 human and 143 animal sera collected on Tutuila island. Over-all, 43.8% of the people sampled had evidence of infection. Sera from 100 adult residents of the same island, collected in 1972, had no Ross River antibody, suggesting recent introduction of the virus. In contrast to the human serological data, the prevalence of Ross River antibodies among animals was relatively low. Dogs and pigs had the highest rates with 20% and 15%, respectively. Results of this study suggest that the Ross River virus cycle during the epidemic in American Samoa involved primarily humans and mosquitoes with animals less frequently infected. These observations plus the recent introduction of Ross River virus into new areas of the South Pacific suggest that a major change has occurred in the epidemiology of epidemic polyarthritis.

Adolescent↗
PubMed1985

Genetic aspects of macrophage involvement in natural resistance to virus infections.

Macrophages are thought to constitute an important element in the body's natural defense against invasion and dissemination of viruses. Possible antiviral mechanisms of macrophages are defined and referred to as intrinsic, i.e. the ability of macrophages to serve as a nonpermissive barrier between the virus and susceptible cells and extrinsic, i.e. the ability of macrophages to affect the virus or virus replication in surrounding cells. Most studies on the role of macrophages in natural resistance to virus infections have been performed in animal models. An interesting aspect of many viral infections in animals is the finding of a genetically determined variation in natural resistance. Because of the availability of numerous inbred and congenic strains most studies on genetically determined resistance have been performed in mice. The classical examples are resistance to flaviviruses and susceptibility to mouse hepatitis virus, both of which are inherited as dominant, monogenic traits. With these viruses macrophage intrinsic restriction of virus replication has been found to express at the cellular level the genetics of resistance/susceptibility seen in the intact animal. Other examples, where macrophages have been implicated in genetically determined resistance include herpes simplex virus and influenza virus. The involvement of macrophages in natural resistance to these viruses is discussed in relation to other putative resistance determinants like interferon production and sensitivity and natural killer cell activity.

Animals↗
PubMed1993

Viruses as teratogens.

The ability of certain viruses to affect prenatal development in domestic animals is well documented. However, differentiating a viral-induced malformation from those caused by genetic or other environmental causes is a diagnostic dilemma. Understanding how viruses interact with their embryo-fetal hosts and the potential consequences on prenatal development requires refining and dispelling some old concepts and injecting new insights into this diagnostic challenge. This article discusses several viral teratogens affecting domestic animals: Akabane, bluetongue, Cache Valley, Japanese B encephalitis, bovine viral diarrhea, Border disease, Chuzan, epizootic hemorrhagic disease, hog cholera, Rift Valley fever, and Wesselsbron disease viruses.

Animals↗
PubMed2003

A novel neurotropic expression vector based on the avirulent A7(74) strain of Semliki Forest virus.

Semliki Forest virus (SFV), an enveloped alphavirus of the family Togaviridae, infects a wide range of mammalian host cells. Most strains are neurotropic but differ in virulence. The authors took advantage of the nonpathogenic properties of SFV strain A7(74), cloned recently in their laboratory, and constructed a replication-proficient expression vector to target the central nervous system (CNS) for heterologous gene expression. The vector, termed VA7, was engineered to drive expression of foreign inserts through a second subgenomic promoter inserted in the viral 3' nontranslated region (NTR). Infectious virus was obtained by in vitro transcription and transfection into BHK cells, and was shown to direct synthesis of heterologous proteins in several mammalian cell lines. Although novel expression vehicle is not applicable for targeting specific cell populations within the CNS in its present form, in cultured rat hippocampal slices, VA7 encoding enhanced green fluorescent protein (EGFP) efficiently transduced pyramidal cells, interneurons, and glial cells. With prolonged time post infection, the number of EGFP-expressing neurons in hippocampal slices increased. Mice infected intraperitoneally with the recombinant virus remained completely asymptomatic but showed CNS expression of EGFP as evidenced by immunohistochemistry. SFV A7(74) is a nonintegrating virus, which gives rise to a randomly distributed, patchy infection of the adult CNS that is cleared within 10 days. With the advantage of noninvasive administration, the expression vector described in this work is thus applicable for short-term gene expression in the CNS.

Animals↗
PubMed1994

Viral infection including HIV and AIDS.

Viruses have long been considered candidates for infectious etiologic agents or cofactors in the development of rheumatic diseases. The current epidemic of HIV infection and the recognition of "emerging viruses" has focused interest on the possible role of viruses in pathogenesis of diseases without defined etiology. Over the past year, the role of parvovirus B19 in chronic arthropathy was further defined. Additional data added to our understanding of the mechanisms by which rubella virus may cause chronic arthritis. We were reminded of the potential the togaviruses have to cause epidemics of febrile arthritis. The developing story of hepatitis C virus in essential mixed cryoglobulinemia encourages us to explore strategies for specific antiviral therapies. The members of the herpesvirus family came under scrutiny for their role in Sjögren's syndrome. The retroviruses continue to attract attention because of rheumatic disease syndromes in AIDS patients and the suggestion that still undefined retroviruses may play an etiologic role in rheumatoid arthritis. This review highlights efforts made in the past year to elucidate the role of viral infection in rheumatologic disease.

Arthritis, Infectious↗
PubMed1993

Gene targeting in human somatic cells. Complete inactivation of an interferon-inducible gene.

The role, if any, of the human interferon-inducible 6-16 gene in the establishment of a cellular antiviral state is unknown. To address this problem, and as part of a wider investigation of homologous recombination (HR) and its applications in somatic cells, we have been using HR to disrupt the 6-16 gene in human cell lines [Itzhaki, J. E. & Porter, A. C. G. (1991) Nucleic Acids Res. 19, 3835-3842.] We describe here the design and use of insertion and replacement-type targeting constructs based on a promoterless bacterial gpt gene that is activated by HR with the 6-16 gene. In HeLa cells, both targeting constructs underwent extrachromosomal HR with a cotransfected plasmid carrying the 6-16 gene. In a previously targeted clone derived from the fibrosarcoma cell line HT1080, the replacement construct underwent HR with either the modified or the unmodified 6-16 allele. The latter events generated doubly disrupted (6-16-/-) clones that failed to express any detectable 6-16 messenger RNA in response to interferon. Plaque assays of infected 6-16-/- cells showed that expression of the 6-16 gene was not required for the induction by interferon of an antiviral state against encephalomyocarditis virus, semliki forest virus or cocal virus.

Base Sequence↗
PubMed2001

Expression of human MxA protein in mosquito cells interferes with LaCrosse virus replication.

Human MxA protein inhibits LaCrosse virus (LAC virus; family Bunyaviridae) replication in vertebrate cells and MxA-transgenic mice. LAC virus is transmitted to humans by Aedes triseriatus mosquitoes. In this report, we have shown that transfected mosquito cells expressing the human MxA cDNA are resistant to LAC virus but permissive for Sindbis virus (family Togaviridae) infection.

Aedes↗
PubMedDate not supplied

Serological cross-reactions against Yersinia enterocolitica in patients infected with other arthritis-associated microbes.

In order to investigate arthritis-triggering, serologically cross-reactive antigens, sera from patients infected with arthritis-associated microbes, Salmonellae, Chlamydia trachomatis, and Sindbis-like alphavirus, were reacted against SDS-PAGE separated and immunoblotted Yersinia enterocolitica 0:3 antigens. These sera reacted with Yersinia to the same extent as did the control sera taken from patients with streptococcal, staphylococcal and Bordetella pertussis infections or from healthy blood donors. Moreover, the various sera produced different reactivity patterns, directed against several different antigens. Although sera from test subjects, as well as from controls including healthy individuals, recognized some Yersinia antigens, these patterns differed markedly from those recognized by sera taken from patients with Yersinia infection. Significantly, analysis of the reactivities against the different molecular weight antigen components of Yersinia revealed no dominant band or pattern which could thus have been defined as arthritis-associated.

Adult↗
PubMed2006

Seroprevalence and distribution of Flaviviridae, Togaviridae, and Bunyaviridae arboviral infections in rural Cameroonian adults.

Arboviruses from the families Flaviviridae, Togaviridae, and Bunyaviridae are suspected to cause widespread morbidity in sub-Saharan African populations, but little research been done to document the burden and distribution of these pathogens. We tested serum samples from 256 Cameroonian adults from nine rural villages for the presence of Dengue-2 (DEN-2), West Nile (WN), Yellow fever (YF), Chikungunya (CHIK), O'nyong-nyong (ONN), Sindbis (SIN), and Tahyna (TAH) infection using standard plaque-reduction neutralization tests (PRNT). Of these samples, 12.5% were DEN-2 positive, 6.6% were WN positive, 26.9% were YF positive, 46.5% were CHIK seropositive, 47.7% were ONN positive, 7.8% were SIN positive, and 36.3% were TAH positive. DEN-2, YF, and CHIK seroprevalence rates were lower among individuals living in dwellings with grass or thatched roofs versus corrugated tin and in villages isolated from urban centers. Seroprevalence rates of YF and CHIK increased with age. These results suggest that inter-epidemic arboviral infection is common in central African populations.

Adolescent↗
PubMed1988

A study of viral and rickettsial exposure and causes of fever in Juba, southern Sudan.

Patients presenting at the Juba Teaching Hospital, either with fever of undetermined origin or with a clinical cause of fever, gave evidence of exposure to a wide range of viral and rickettsial agents. Serological tests showed high antibody levels to flaviviruses (56.9%) and alphaviruses (29.2%), with lesser levels of bunyamweraviruses (3.8%), Rift Valley fever (2.3%), and sandfly fever (0.75%). Flavivirus exposure was significantly associated with clinical evidence of liver disease; repeated exposure to flaviviruses was particularly prevalent in those with poor sanitation and who had received previous injections. A significant focus of Ebola and Marburg exposure in Juba has been identified. Clinical evidence of liver disease was evident in 37% of patients studied, and 24.6% were HBsAg positive. The first 2 HIV-positive individuals from the southern Sudan are reported, including one with clinical AIDS. A high prevalence of positive antibodies to Rickettsia typhi in the population indicated that murine typhus was common locally. This study indicates the need for further public health measures in the southern Sudan to control the spread of these infections.

Adolescent↗
PubMedDate not supplied

[O'NYONG-NYONG FEVER].

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Arbovirus Infections↗