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Infection of macaques with chimeric simian/human immunodeficiency virus (SHIV) expressing the envelope protein of HIV-1 provides a model system for studying HIV-1 infection in humans. To this end, four rhesus macaques (Macaca mulatta) were given a single intravaginal (IVAG) inoculation of cell-free SHIV SF33A and longitudinal samples of peripheral blood and lymph nodes were analyzed for viremia,...
Myxoma virus was introduced into the European rabbit population of Australia in 1950. Although the virus was initially highly lethal in rabbits, there was rapid selection for less virulent strains of virus and innately resistant rabbits. To investigate the basis of resistance to myxoma virus, we have compared the pathogensis of the virulent strain of myxoma virus originally released into Australia...
Mechanisms of acute retroviral pathogenesis have been examined during primary infection of rhesus macaques with simian–human immunodeficiency virus 89.6PD (SHIV 89.6PD ). During acute infection, between initial exposure and establishment of antigen-specific immune responses that stabilize the virus burden, rapid immune system changes influence the viral set-point and dictate subsequent steps...
Coreceptor utilization by HIV-1 is an important determinant of pathogenesis. However, coreceptor selectivity is defined in vitro, while in vivo critical pathogenic events occur in lymphoid tissues. Using pharmacological inhibitors, we recently provided evidence that coreceptor selectivity by the R5X4 dual-tropic isolate 89.6 was more restricted in ex vivo infected lymphoid tissue than in vitro [S...
A quantitative RT–PCR assay was developed for SIVagm and was used to measure the levels of viral RNA in the plasma of experimentally and naturally infected African green monkeys. The number of productively infected PBMCs and the number of cells carrying integrated provirus were also measured. Plasma virus loads in experimentally infected animals peaked at 2 weeks postinfection, ranging from 2.9 ×...
The course of Venezuelan equine encephalitis (VEE) disease in immunodeficient and immunologically normal mice was compared to define the role of the immune system in this disease process. Immunocompetent mice infected with VEE exhibited a biphasic illness characterized by an early self-limiting lymphoid phase and a fatal CNS phase. The lymphoid phase of the illness was characterized by extensive viral...
NF-κB comprises a family of transcription factors that regulate key immune processes. In this study, the effects of orthopoxvirus infection upon the activation of NF-κB were examined. During the early phase of infection, cowpox virus can inhibit the induction of NF-κB-regulated gene expression by interfering with the process of IκBα degradation. Although either okadaic acid or tumor necrosis factor...
Infections with coxsackievirus B3 (CVB3) are common causes of myocarditis in humans. One detail of CVB3-induced pathogenesis is apoptosis. The interaction between the capsid protein VP2 of the myocardial virus variant CVB3H3 and the proapoptotic host cell protein Siva has recently been observed. In order to characterize the interaction between both proteins more precisely, the binding activity of...
Studies of the pathogenesis of dengue hemorrhagic fever (DHF), a potentially life-threatening disease, have revealed the importance of initial high levels of virus replication. However, the possible involvement of virus during the transition from fever to defervescence, a critical stage in determining the severity of disease, has not been appreciated. Using quantitative reverse transcription-polymerase...
A mouse-adapted strain of Ebola Zaire virus produces a fatal infection when BALB/cj mice are infected intraperitoneally (ip) but subcutaneous (sc) infection with the same virus fails to produce illness and confers long-term protection from lethal ip rechallenge. To identify immune correlates of protection in this model, we compared viral replication and cytokine/chemokine responses to Ebola virus...
In vivo, human immunodeficiency virus type 2 (HIV-2) infection reveals several unique characteristics when compared to HIV-1 infection, the most remarkable of which is the extraordinarily long asymptomatic period. Here we describe two HIV-2 primary isolates, obtained from asymptomatic individuals, which do not infect any coreceptor-expressing cell lines tested. In those cells, we show that the absence...
Pathogenicity was reportedly restored to an avirulent molecular clone of equine infectious anemia virus (EIAV) by substitution of 3' sequences from the pathogenic variant strain (EIAV PV ). However, the incidence of disease in horses/ponies was found to be significantly lower (P = 0.016) with the chimeric clone (EIAV UK ) than with EIAV PV . This was attributable...
Sendai virus V protein is not essential for virus replication in cultured cells but is essential for efficient virus replication and pathogenesis in mice, indicating that the V protein has a luxury function to facilitate virus propagation in mice. This was discovered in the Z strain, an egg-adapted avirulent laboratory strain. In the present study, we reexamined the function of Sendai virus V protein...
Recent findings support an indirect relationship between T cell depletion in HIV-1 infection and the rate of virus replication with implications for treatment strategies. We have initiated a new approach to recover immune function through the use of novel chemical agents. A cationic amphiphilic drug that binds to Ca 2+ -calmodulin at high concentrations, [10-{3-(4-methyl-1-piperazinyl)-propyl}-2-...
Viral loads were investigated in SIVmnd-1 chronically infected mandrills and the results were compared with those previously observed in other nonpathogenic natural SIV infections. Four naturally and 11 experimentally SIVmnd-1-infected mandrills from a semi-free-ranging colony were studied during the chronic phase of infection. Four SIVmnd-1-infected wild mandrills were also included for comparison...
Sindbis virus virions incorporating uncleaved precursor envelope protein PE2 bind efficiently to cell-surface heparan sulfate (HS) because the furin cleavage site (a consensus HS-binding domain) is retained in the mature virus particle. However, they are essentially nonviable. Resuscitating mutations selected in the E3 or E2 protein preserve the PE2 noncleaving phenotype and HS binding, but facilitate...
Retroviruses, such as human and simian immunodeficiency viruses (HIV and SIV), and murine leukemia viruses (MuLV), harbor a tyrosine-based motif in the intracytoplasmic domain of their envelope glycoprotein. This motif can act as an endocytosis signal or as a targeting signal, restricting viral budding at specific cell surface membrane domains. In the present study, proviral DNA of the ecotropic Cas-Br-E...
Loss of T cell homeostasis usually precedes the onset of AIDS. We hypothesized that rapid progressors may be transmitted with HIV-1 that is particularly able to perturb T cell homeostasis. To this end, we have tested two transmitted, syncytium-inducing (SI) viral isolates from a rapid progressor in two thymus models. One of the isolates (R3A) exhibited markedly rapid kinetics of replication and thymocyte...
The early pathogenesis of Marek's disease virus (MDV) infection is characterized by a lytic infection followed by the induction of latency. Genetically resistant N2a and susceptible P2a chickens were infected with the less virulent JM-16 or the very virulent plus (vv+) RK-1 MDV strains to examine the relationship between virulence and resistance on virus replication during 1–10 days postinfection...
We previously described a thymus-tropic HIV-1 envelope (R3A Env) from a rapid progressor obtained at the time of transmission. An HIV-1 molecular recombinant with the R3A Env supported extensive replication and pathogenesis in the thymus and did not require Nef. Another Env from the same patient did not display the same thymus-tropic pathogenesis (R3B Env). Here, we show that relative to R3B Env,...
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