Latent herpesviruses of humans

The herpesviruses that infect humans characteristically establish a latent infection that may be reactivated later. The consequences of reactivation range from asymptomatic shedding to severe disseminated infection. Varicella-zoster and herpes simplex viruses are both highly neurotropic, establishing nonreplicating infections in sensory ganglia. Latent herpes simplex virus is known to reside in neurons, and the virus-cell interactions involved have been defined to an extent. Cytomegalovirus and Epstein-Barr virus interact with peripheral blood leukocytes. Latent cytomegalovirus infection of human leukocytes has not been proved, although studies in a murine model have implicated B lymphocytes as a repository of latent virus. Epstein-Barr virus is known to persist in a non-replicating state as extrachromosomal DNA in B lymphocytes and to cause "immortalization" of the infected cell; persistence of the viral genome in epithelial cells may also result in malignant transformation, such as nasopharyngeal carcinoma.     

Dermatomyositis and HIV infection: case report and review of the literature

Since the 1980s, a host of autoimmune phenomena and rheumatologic illnesses have been linked to infection with the human immunodeficiency virus (HIV). Given the broad effects of this virus on both the humoral and cell-mediated arms of the immune system, illnesses such as polymyositis and Reiter’s syndrome appear to be more prevalent in HIV-infected individuals and occur in the absence of well-described predispositions. The activities of some rheumatologic illnesses exhibit an inverse relationship with the course of HIV infection, such as rheumatoid arthritis, which becomes more quiescent with advancing disease. Dermatomyositis is a rheumatologic illness that very infrequently occurs and during our review of literature only three other cases were reported. We present the case of a Caucasian male in his mid-20s who presented with acquired immunodeficiency syndrome and subsequently developed dermatomyositis. In this review, we highlight the current relationship between HIV infection and autoimmunity, the possible ways HIV infection may foster an environment favorable for the development of dermatomyositis, and review the previously reported cases of individuals with HIV infection who developed dermatomyositis. The complex issues of how to treat individuals with HIV and dermatomyositis is also discussed.     

Heterogeneity of the association between lower respiratory illness in infancy and subsequent asthma

Viral lower respiratory tract illnesses occurring during the first years of life are associated with increased risk of subsequent asthma, but the mechanisms involved have not been completely elucidated. The available evidence suggests that the factors that explain this connection are heterogeneous. Children who start life with lower levels of airway function appear to be more prone to transient forms of wheezing in the first years of life. "Intrinsic" bronchial hyperresponsiveness, that is, that measured shortly after birth and unrelated to markers of atopy, has been reported to predict both early life wheezing and wheezing occurring during the early school years, independent of atopy. It has also been suggested that both decreased interferon-gamma responses measured before any viral lower respiratory illness and increased interferon-gamma responses measured at the time of the illness may predispose to such illnesses. Children in whom the former mechanism is involved should be expected to be more atopic later in life, whereas those with the latter mechanism should be less likely to be atopic. This may explain why early viral respiratory illnesses have been found to be both protective against and a risk factor for subsequent atopy in different studies. Current evidence thus suggests that different and often apparently contradictory mechanisms related to airway function, structure, and immune responsiveness may explain the association between viral lower airway illness in early life and subsequent asthma. Future preventive and therapeutic strategies will need to address the specific mechanisms that explain this association in different groups of subjects.     

The role of viruses in development or exacerbation of atopic asthma

Respiratory viral infections in early childhood have been linked to the development of persistent wheezing and asthma. Epidemiologic data indicate that, for the majority of children, virus-induced wheezing is a self-limited condition, with no long-term consequences. For a substantial minority, however, virus-induced wheezing is associated with persistent asthma and the potential for enhanced allergic sensitization. For the most part, this subset of patients is genetically predisposed; they are atopic children in whom respiratory viral infections trigger the early development of asthma by mechanisms that have not been fully elucidated. Both inflammatory and noninflammatory mechanisms may be involved. It does not appear that viral infection per se in early life is responsible for the induction of atopic asthma. Data from animal models provide support for the concept that enhanced allergic sensitization caused by increased uptake of allergen during infection may play a critical role, as well as T-cell-mediated immune responses to viral infection, which may favor eosinophilic inflammatory responses and the development of altered airway function to inhaled methacholine. Recent advances in our understanding of the interactions between respiratory viruses and the development of reactive airway disease offer new possibilities for preventive treatment in children at risk for developing persistent wheezing and asthma exacerbation as a result of viral infection.     

Immunopathogenesis: role of innate and adaptive immune responses

Hepatitis B virus (HBV) infection in immunocompetent adults usually results in a self-limited, transient liver disease and viral clearance, with only a small percentage (5 to 10%) developing chronic hepatitis associated with viral persistence. In contrast, when neonates are infected, more than 90% become persistently infected, suffering differing degrees of chronic liver disease. Activation of immunity plays a central role in host-virus interactions, greatly influencing viral replication and the clinical outcome of infection. Although all of the specific mechanisms and consequences of this interaction have not been elucidated, the purpose of this article is to describe the basic arms of the immune system as they interact with the HBV and describe the present state of knowledge in this area. These arms may be divided broadly into innate and specific immune responses, and they have different roles and responses in acute and chronic infection.     

Innate Immunity and Immune Evasion by Enterovirus 71

Enterovirus 71 (EV71) is a major infectious disease affecting millions of people worldwide and it is the main etiological agent for outbreaks of hand foot and mouth disease (HFMD). Infection is often associated with severe gastroenterological, pulmonary, and neurological diseases that are most prevalent in children. Currently, no effective vaccine or antiviral drugs exist against EV71 infection. A lack of knowledge on the molecular mechanisms of EV71 infection in the host and the virus-host interactions is a major constraint to developing specific antiviral strategies against this infection. Previous studies have identified and characterized the function of several viral proteins produced by EV71 that interact with the host innate immune proteins, including type I interferon signaling and microRNAs. These interactions eventually promote efficient viral replication and increased susceptibility to the disease. In this review we discuss the functions of EV71 viral proteins in the modulation of host innate immune responses to facilitate viral replication.     

The impact of steatosis and alcohol on hepatitis C

Alcohol consumption and hepatic steatosis interact synergistically with hepatitis C virus (HCV) to accelerate fibrosis progression and reduce the efficacy of standard antiviral therapies. Research aimed at delineating the viral and host interactions involved in the pathogenesis of steatosis in HCV infection may provide novel therapeutic strategies that can modify disease progression and improve treatment response. This review discusses the clinical aspects of HCV fibrosis progression and treatment response in the setting of alcohol use or hepatic steatosis.     

Steatosis and chronic hepatitis C virus infection: mechanisms and significance

Chronic hepatitis C (CHC) and steatosis are common entities that have the potential to interact synergistically and result in significant morbidity. Steatosis is frequently observed in CHC and seems to have a significant impact on the natural history of the disease with respect to development of fibrosis and reducing the virologic response to current therapy. Research efforts should continue to focus on delineating the complex viral and host interactions involved in the pathogenesis of hepatitis C virus (HCV)-related steatosis. This may provide novel future therapeutic strategies that may help modulate disease progression in relation to steatosis in HCV infection.     

Identification of Cellular Proteins that Interact with Human Cytomegalovirus Immediate-Early Protein 1 by Protein Array Assay

Human cytomegalovirus (HCMV) gene expression during infection is characterized as a sequential process including immediate-early (IE), early (E), and late (L)-stage gene expression. The most abundantly expressed gene at the IE stage of infection is the major IE (MIE) gene that produces IE1 and IE2. IE1 has been the focus of study because it is an important protein, not only for viral gene expression but also for viral replication. It is believed that IE1 plays important roles in viral gene regulation by interacting with cellular proteins. In the current study, we performed protein array assays and identified 83 cellular proteins that interact with IE1. Among them, seven are RNA-binding proteins that are important in RNA processing; more than half are nuclear proteins that are involved in gene regulations. Tumorigenesis-related proteins are also found to interact with IE1, implying that the role of IE1 in tumorigenesis might need to be reevaluated. Unexpectedly, cytoplasmic proteins, such as Golgi autoantigen and GGA1 (both related to the Golgi trafficking protein), are also found to be associated with IE1. We also employed a coimmunoprecipitation assay to test the interactions of IE1 and some of the proteins identified in the protein array assays and confirmed that the results from the protein array assays are reliable. Many of the proteins identified by the protein array assay have not been previously reported. Therefore, the functions of the IE1-protein interactions need to be further explored in the future.     

HIV and hepatitis virus infection

As the life expectancy of patients with HIV infection increases, greater attention will need to be focused on concurrent illnesses, such as viral hepatitis, that may increase mid- to long-range morbidity and mortality. The incidence of viral hepatitis is increased in patients with HIV disease, reflecting the epidemiologic risks that these two conditions share. Coinfection with HIV seems to adversely affect the natural history of hepatitis C but may actually reduce the hepatic damage associated with hepatitis B. Immunosuppression due to HIV does not seem to significantly affect hepatitis A, E, or G. Clinicians have been reluctant to treat viral hepatitis in the HIV-infected population, but this therapeutic nihilism is unwarranted. Most studies have concluded that the treatment of hepatitis C in HIVinfected patients results in an initial efficacy and a long-term response similar to those seen in the HIV-seronegative population. Although the efficacy of interferon is reduced against hepatitis B, some nucleoside analogues are effective.     

HIV and hepatitis virus infection

As the life expectancy of patients with HIV infection increases, greater attention will need to be focused on concurrent illnesses, such as viral hepatitis, that may increase mid- to long-range morbidity and mortality. The incidence of viral hepatitis is increased in patients with HIV disease, reflecting the epidemiologic risks that these two conditions share. Coinfection with HIV seems to adversely affect the natural history of hepatitis C but may actually reduce the hepatic damage associated with hepatitis B. Immunosuppression due to HIV does not seem to significantly affect hepatitis A, E, or G. Clinicians have been reluctant to treat viral hepatitis in the HIV-infected population, but this therapeutic nihilism is unwarranted. Most studies have concluded that the treatment of hepatitis C in HIV-infected patients results in an initial efficacy and a long-term response similar to those seen in the HIV-seronegative population. Although the efficacy of interferon is reduced against hepatitis B, some nucleoside analogues are effective.     

HIV and hepatitis virus infection

As the life expectancy of patients with HIV infection increases, greater attention will need to be focused on concurrent illnesses, such as viral hepatitis, that may increase mid- to long-range morbidity and mortality. The incidence of viral hepatitis is increased in patients with HIV disease, reflecting the epidemiologic risks that these two conditions share. Coinfection with HIV seems to adversely affect the natural history of hepatitis C but may actually reduce the hepatic damage associated with hepatitis B. Immunosuppression due to HIV does not seem to significantly affect hepatitis A, E, or G. Clinicians have been reluctant to treat viral hepatitis in the HIV-infected population, but this therapeutic nihilism is unwarranted. Most studies have concluded that the treatment of hepatitis C in HIV-infected patients results in an initial efficacy and a long-term response similar to those seen in the HIVseronegative population. Although the efficacy of interferon is reduced against hepatitis B, some nucleoside analogues are effective.     

Vasculitis and infection with the human immunodeficiency virus

Vasculitic syndromes associated with infection with the human immunodeficiency virus (HIV) would appear to represent a microcosm of the vasculitic spectrum. Reported cases have included polyarteritis nodosa-like illnesses, hypersensitivity vasculitis, lymphomatoid granulomatosis, primary angiitis of the central nervous system, and a number of miscellaneous disorders. The pathogenesis of these conditions is unclear, but some appear to be mediated in part by the HIV itself. Therapeutically, little clinical data exist to guide clinicians in the management of such patients, but aggressive approaches combining immunosuppressive therapy with assertive antimicrobial prophylaxis may be warranted.     

Expression of hepatitis C virus proteins does not interfere with major histocompatibility complex class I processing and presentation in vitro

Hepatitis C virus (HCV) infection takes a chronic course in the majority of patients. The mechanisms underlying the evasion of the host immune response and viral persistence are poorly understood. In this context, we investigated interactions of HCV proteins with major histocompatibility complex (MHC) class I processing and presentation pathways using cell lines that allow the tetracycline-regulated expression of viral structural and nonstructural proteins. These well-characterized inducible cell lines were found to efficiently process and present endogenously synthesized HCV proteins via MHC class I. Functional MHC class I cell-surface expression and intracellular proteasome activity were not affected by the expression of HCV proteins. These results suggest that viral evasion of the host immune response does not involve interactions of HCV with MHC class I processing and presentation. Other mechanisms, such as interference with the interferon system, may be operative in HCV infection, leading to viral persistence.     

Plasma lactoferrin content: differential effect of steroid administration and infective illnesses: lack of effect of ambient temperature at which specimens are collected

The effect of parenteral hydrocortisone on plasma lactoferrin concentration, neutrophil count and lactoferrin:neutrophil ratio was assessed in 10 volunteer subjects. Administration of a single dose of corticosteroid was followed by a significant rise in the circulating neutrophil count, a significant but proportionately smaller rise in the plasma lactoferrin concentration and a significant fall in the lactoferrin:neutrophil ratio. Acute viral infections were found to be associated with a disproportionately low plasma lactoferrin concentration relative to the circulating neutrophil count. The relatively low lactoferrin concentrations in both these situations could be of significance in regard to the propensity to bacterial infection and superinfection which these 2 groups of subjects display. Compared to patients with viral infection, those suffering from Plasmodium falciparum malaria showed a significantly elevated lactoferrin:neutrophil ratio, although this ratio was not significantly different when malarial patients were compared to normal individuals. These findings suggest that the pathogenesis of relative neutropenia in viral and protozoal illnesses is fundamentally different. Finally, it was found that the temperature at which specimen collection takes place does not appear to be a significant variable determining the plasma lactoferrin concentration.     

Actin' up: herpesvirus interactions with Rho GTPase signaling

Herpesviruses constitute a very large and diverse family of DNA viruses, which can generally be subdivided in alpha-, beta- and gammaherpesvirus subfamilies. Increasing evidence indicates that many herpesviruses interact with cytoskeleton-regulating Rho GTPase signaling pathways during different phases of their replication cycle. Because of the large differences between herpesvirus subfamilies, the molecular mechanisms and specific consequences of individual herpesvirus interactions with Rho GTPase signaling may differ. However, some evolutionary distinct but similar general effects on Rho GTPase signaling and the cytoskeleton have also been reported. Examples of these include Rho GTPase-mediated nuclear translocation of virus during entry in a host cell and Rho GTPase-mediated viral cell-to-cell spread during later stages of infection. The current review gives an overview of both general and individual interactions of herpesviruses with Rho GTPase signaling.     

Relationships between lymphomas linked to hepatitis C virus infection and their microenvironment

The relationships between lymphomas and their microenvironment appear to follow 3 major patterns:(1)an independent pattern;(2)a dependent pattern on deregulated interactions;and(3)a dependent pattern on regulated coexistence.Typical examples of the third pattern are hepatitis C virus(HCV)-associated marginal zone lymphomas(MZLs)and mucosa-associated lymphoid tissue lymphomas.In these lymphomas,a regulated coexistence of the malignant cells and the microenvironmental factors usually occurs.At least initially,however,tumor development and cell growth largely depend on external signals from the microenvironment,such as viral antigens,cytokines,and cell-cell interactions.The association between HCV infection and B-cell lymphomas is not completely defined,although this association has been demonstrated by epidemiological studies.MZL and diffuse large B-cell lymphoma are the histotypes most frequently associated with HCV infection.Many mechanisms have been proposed for explaining HCV-induced lymphomagenesis;antigenic stimulation by HCV seems to be fundamental in establishing B-cell expansion as observed in mixed cryoglobulinemia and in B-cell lymphomas.Recently,antiviral treatment has been proved to be effective in the treatment of HCV-associated indolent lymphomas.Importantly,clinically responses were linked to the eradication of the HCV-RNA,providing a strong argument in favor of a causative link between HCV and lymphoproliferation.