Hantaviruses are tri-segmented negative sense single stranded RNA viruses that belong to the family Bunyaviridae. In nature, hantaviruses are exclusively maintained in the populations of their specific rodent hosts. In their natural host species, hantaviruses usually develop a persistent infection with prolonged virus shedding in excreta. Humans become infected by inhaling virus contaminated aerosol. Unlike asymptomatic infection in rodents, hantaviruses cause two acute febrile diseases in humans: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). The mortality rate varies from 0.1% to 40% depending on the virus involved. Hantaviruses are distributed world wide, with over 150,000 HFRS and HPS cases being registered annually. In this review we summarize current knowledge on hantavirus molecular biology, epidemiology, genetic diversity and co-evolution with rodent hosts. In addition, special attention was given in this review to describing clinical manifestation of HFRS and HPS, and advances in our current understanding of the host immune response, treatment, and prevention.

In this study we present the characterization of a novel transcript, UL81-82ast, UL81-82 antisense transcript, and its protein product. The transcript was initially found in a cDNA library of monocytes from a seropositive donor. mRNA was obtained from monocytes isolated from a healthy donor with a high antibody titer against human cytomegalovirus (HCMV). The mRNAs were cloned into a lambda phage-derived vector to create the cDNA library. Using PCR, UL81-82ast was amplified from the library. The library was tested for the presence of numerous HCMV genes. Neither structural genes nor immediate-early genes were found. UL81-82ast was detected in five bone marrow samples from healthy antibody-positive donors. This same transcript was also found in in vitro-infected human fibroblasts early after infection but disappears at the same time that UL82 transcription begins. Not only was the transcript amplified using reverse transcription-PCR and sequenced but its protein product (UL82as protein) was detected by both Western blot and immunofluorescence. Phylogenetic studies using UL82as protein were conducted, showing a high degree of conservation in clinical isolates, laboratory strains of HCMV, and even in chimpanzee CMV. The transcript could be involved in the posttranscriptional regulation of the UL82 gene, affecting its mRNA stability or translation. Since the UL82 product, pp71, functions as an immediate-early transactivator, its posttranscriptional control could have some effect over latency reactivation and lytic replication.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease characterized by chronic brain inflammation. Leukocyte infiltration of brain tissue causes inflammation, demyelination, and the subsequent formation of sclerotic plaques, which are a hallmark of MS. Activation of proinflammatory cytokines is essential for regulation of lymphocyte migration across the blood–brain barrier. We demonstrate increased levels of many cytokines, including IL-2RA, CCL5, CCL11, MIF, CXCL1, CXCL10, IFNγ, SCF, and TRAIL, were upregulated in cerebrospinal fluid (CSF), whereas IL-17, CCL2, CCL3, CCL4, and IL-12(p40) were activated in MS serum. Interaction analysis of cytokines in CSF demonstrated a connection between IFNγ and CCL5 as well as MIF. Many cells can contribute to production of these cytokines including CD8 and Th1 lymphocytes and astrocytes. Therefore, we suggest that IFNγ released by Th1 lymphocytes can activate astrocytes, which then produce chemoattractants, including CCL5 and MIF. These chemokines promote an inflammatory milieu and interact with multiple chemokines including CCL27 and CXCL1. Of special note, upregulation of CCL27 was found in CSF of MS cases. This observation is the first to demonstrate CCL27 as a potential contributor of brain pathology in MS. Our data suggest that CCL27 may be involved in activation and migration of autoreactive encephalitogenic immune effectors in the brain. Further, our data support the role of Th1 lymphocytes in the pathogenesis of brain inflammation in MS, with several cytokines playing a central role.

Previous data indicate that immune mechanisms may be involved in developing capillary leakage during Sin Nombre virus (SNV) infection. Therefore, we investigated production of tumor necrosis factor alpha (TNF-␣) by human alveolar macrophages and human umbilical vein endothelial cells (HUVEC) after infection with SNV. In addition, we examined the effect of TNF-␣ on HUVEC monolayer leakage. Our results reveal that although TNF-␣ decreases accumulation of viral nucleoproteins, TNF-␣ levels do not change in SNV-infected cells. In addition, supernatants from SNV-infected human alveolar macrophages did not cause a significant increase in endothelial monolayer permeability.

Our study of the changes in cytokine profile in blood serum and in the spinal cord after traumatic spinal cord injury (SCI) has shown that an inflammatory reaction and immunological response are not limited to the CNS, but widespread. This fact was confirmed by changes detected in a cytokine profile in blood serum samples [MIP-1α, interleukin 1 (IL-1) α, IL-2, IL-5, IL-1β, MCP-1, RANTES]. There were also changes in the levels of MIP-1α, IL-1α, IL-2, IL-5, IL-18, GM-colony-stimulating factor, IL-17α, IFN-γ, IL-10, IL-13, MCP-1, and GRO KC CINC-1 in samples of the rat injured spinal cord. The results underscore the complex cytokine network imbalance exhibited after SCI and show significant changes in the concentrations of 14 cytokines/chemokines with different inflammatory and immunological activities.