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Feline leukemia virus was identified as a cause of disease of the immune system in cats long before the recognition of AIDS in humans. This virus is now considered to be a potentially useful model for the study of how retroviruses affect the immune system. Some isolates of feline leukemia virus (FeLV) cause a depletion of CD4+ T cells after a long latency period, followed by weight loss, diarrhea, and opportunistic infections. In other words, cat or feline AIDS develops. The feline leukemia virus AIDS model (FeLV-FAIDS) was used to investigate the effects of zidovudine in combination with the biological response modifiers, alpha interferon and interleukin-2. Alpha interferon or interleukin-2 alone had no effect on infection with FeLV-FAIDS, but it was found that the addition of alpha interferon to zidovudine treatment resulted in a 25 to 30 percent increase in antiviral activity. In the experimental model, it is also possible to do studies which are not possible in humans; for example, treatment may be started prior to infection with the virus. When a six-week treatment protocol with zidovudine alone or zidovudine with alpha interferon was begun 24 hours prior to injection with the virus, it was found that the animals never developed antigenemia, even after the treatment was ended. (Antigenemia, or the appearance of molecules from the virus in the blood, is a measure of infection in both cats and humans.) However, even in the cats which never developed signs of infection, the presence of infectious virus in bone marrow could still be demonstrated in the laboratory. These results confirm the improved effectiveness of zidovudine when combined with alpha interferon, an effect which may be used to reduce the necessary dosage of the toxic zidovudine. Furthermore, the results provide yet another indication that the earlier antiviral treatment is begun, the more effective it can be in treating the AIDS virus. (Consumer Summary produced by Reliance Medical Information, Inc.)

Vector-borne viruses are naturally transmitted when a vector salivates during feeding on a vertebrate host. Most laboratory studies of infection disregard the role that the vector plays in the pathogenesis of the virus. In this study, intradermal inoculations of Aedes aegypti salivary gland extract (SGE) and Sindbis virus (SINV) were used to investigate the effect of mosquito feeding on the vertebrate immune response to infection with an arthropod-borne virus. Murine cytokine expression in the skin was quantified by means of real-time RT-PCR. In response to co-inoculation of SINV with SGE, interferon (IFN)-β expression at 24 and 72 h post inoculation was significantly reduced by 2.2- and 2.3-fold, respectively, when compared to injection of virus alone. IFN-γ expression in response to SINV infection was significantly decreased by 1.6-fold at 24 h post inoculation when SGE was co-inoculated. In contrast, interleukin (IL)–4 expression was significantly up regulated when SGE was co-inoculated at 24 h post inoculation becoming a 3.3-fold increase by 72 h post inoculation. Compared to expression with SINV alone, IL-10 expression showed a 7.6-fold increase by 72 h post inoculation in mice receiving SGE concurrently with virus. This study suggests that the response to virus is significantly different when an infection is initiated in the presence of mosquito salivary factors, and we identify a possible mechanism for potentiation of viral infections initiated by the natural mosquito vector or in the presence of mosquito saliva.

ABSTRACTClinical isolates of Borrelia burgdorferisensu stricto have been categorized into disseminated and nondisseminated groups based on distinct ribosomal spacer restriction fragment length polymorphism genotypes (RSTs). In order to determine whether transmission by tick bite would alter the dissemination dynamics and disease produced by distinct genotypes, disseminated isolates (RST1), nondisseminated isolates (RST3), and a standard laboratory strain (B-31) were established in a murine cycle utilizing infections transmitted by ticks. B-31 spirochetes circulated in the blood of inbred C3H/HeJ mice longer than in the blood of outbred mice. The majority of C3H mice exposed to RST1-infected ticks contained cultivable spirochetes in their blood for up to 17 days; in contrast, mice exposed to RST3 isolates demonstrated a precipitous decline in infection after day 7 postexposure. A quantitative PCR (q-PCR) assay demonstrated that the densities of spirochetes in blood were similar for the RST1 and RST3 isolates, except during the 2nd week postexposure, when the RST1 isolates displayed a markedly higher density in blood. Spirochete load in the heart and bladder of infected mice was measured by q-PCR at 8 weeks postexposure; the numbers of spirochetes in these tissues were similar for mice infected with either disseminated or nondisseminated strains. Similarly, histopathology samples of heart, bladder, and joint tissue obtained at 8 weeks postexposure did not reveal greater pathology in mice infected with the disseminated isolates. We conclude that although the spirochetemia induced by tick-transmitted disseminated isolates was more intense and of longer duration than that induced by nondisseminated isolates, the resultant pathologies produced by these strains were ultimately similar.

ABSTRACTA multiplex real-time PCR assay was developed for the simultaneous detection of Anaplasma phagocytophilumand Borrelia burgdorferi. The assay was tested on various Anaplasma, Borrelia, Erhlichia, and Rickettsiaspecies, as well as on Bartonella henselaeand Escherichia coli, and the assay was found to be highly specific for A. phagocytophilumand the Borreliaspecies tested (B. burgdorferi, B. parkeri, B. andersonii, and B. bissettii). The analytical sensitivity of the assay is comparable to that of previously described nested PCR assays (A. phagocytophilum, 16S rRNA; B. burgdorferi, flagene), amplifying the equivalent of one-eighth of an A. phagocytophilum-infected cell and 50 borrelia spirochetes. The dynamic range of the assay for both A. phagocytophilumand B. burgdorferiwas =4 logs of magnitude. Purified DNA from A. phagocytophilumand B. burgdorferiwas spiked into DNA extracted from uninfected ticks and from negative control mouse and human bloods, and these background DNAs were shown to have no significant effect on sensitivity or specificity of the assay. The assay was tested on field-collected Ixodes scapularisticks and shown to have 100% concordance compared to previously described non-probe-based PCR assays. To our knowledge, this is the first report of a real-time multiplex PCR assay that can be used for the simultaneous and rapid screening of samples for A. phagocytophilumand Borreliaspecies, two of the most common tick-borne infectious agents in the United States.