Prion infection

The prion infection is a conversion of host encoded prion protein (PrP) from its cellular isoform PrPC into the pathological and infectious isoform PrPSc; the conversion process was investigated by in vitro studies using recombinant and cellular PrP and natural PrPSc. We present a brief summary of the results determined with our in vitro conversion system and the derived mechanistic models. We describe well characterized intermediates and precursor states during the conversion process, kinetic studies of spontaneous and seeded fibrillogenesis and the impact of the membrane environment.     

Nipah virus infection

Nipah virus (NiV), emerged in Peninsular Malaysia, caused an outbreak of severe febrile encephalitis in humans and respiratory diseases in pigs between 1998 and 1999. By May of 1999, the death of 105 humans and the culling of about 1.1 million pigs were reported. Fruitbats of Pteropid species were identified as the natural reservoir hosts. The epidemiological studies suggested that NiV was introduced into pig farms by fruitbats, and was than transmitted to humans (mainly pig farmers) and other animals such as dogs, cats and horses. In 2004, NiV reappeared in Bangladesh with greater lethality. In contrast to the Malaysia case, epidemiologic characteristics of this outbreak suggested the possibility of fruitbats-to-person, or person-to-person transmission. In this article, the epidemiological comparison between two outbreaks in Malaysia and Bangladesh, and the new-trends of virological studies of NiV will be discussed.     

Glutathione and infection

Background

The tripeptide γ-glutamylcysteinylglycine or glutathione (GSH) has demonstrated protective abilities against the detrimental effects of oxidative stress within the human body, as well as protection against infection by exogenous microbial organisms.

Scope of review

In this review we describe how GSH works to modulate the behavior of many cells including the cells of the immune system, augmenting the innate and the adaptive immunity as well as conferring protection against microbial, viral and parasitic infections. This article unveils the direct antimicrobial effects of GSH in controlling Mycobacterium tuberculosis (M. tb) infection within macrophages. In addition, we summarize the effects of GSH in enhancing the functional activity of various immune cells such as natural killer (NK) cells and T cells resulting in inhibition in the growth of M. tb inside monocytes and macrophages. Most importantly we correlate the decreased GSH levels previously observed in individuals with pulmonary tuberculosis (TB) with an increase in the levels of pro-inflammatory cytokines which aid in the growth of M. tb.

Major conclusions

In conclusion, this review provides detailed information on the protective integral effects of GSH along with its therapeutic effects as they relate to the human immune system and health.

General significance

It is important to note that the increases in the levels of pro-inflammatory cytokines are not only detrimental to the host due to the sequel that follow such as fever and cachexia, but also due to the alteration in the functions of immune cells. The additional protective effects of GSH are evident after sequel that follows the depletion of this antioxidant. This is evident in a condition such as Cystic Fibrosis (CF) where an increased oxidant burden inhibits the clearance of the affecting organism and results in oxidant-induced anti-protease inhibition. GSH has a similar protective effect in protozoans as it does in human cells. Thus GSH is integral to the survival of some of the protozoans because some protozoans utilize the compound trypanothione [T(SH)₂] as their main antioxidant. T(SH)₂ in turn requires GSH for its production. Hence a decrease in the levels of GSH (by a known inhibitor such as buthionine sulfoximine [BSO] can have adverse effects of the protozoan parasites. This article is part of a Special Issue entitled Cellular functions of glutathione.     

Burkholderia cenocepacia infection

Phagocytosis is an important component of innate immunity that contributes to the eradication of infectious microorganisms; however, successful bacterial pathogens often evade different aspects of host immune responses. A common bacterial evasion strategy entails the production of toxins and/or effectors that disrupt normal host cell processes and because of their importance Rho-family GTPases are often targeted. Burkholderia cenocepacia, an opportunistic pathogen that has a propensity to infect cystic fibrosis patients, is an example of a pathogenic bacterium that has only recently been shown to disrupt Rho GTPase function in professional phagocytes. More specifically, B. cenocepacia disrupts Rac and Cdc42 seemingly through perturbation of guanine nucleotide exchange factor function. Inactivation of Rac, Cdc42 and conceivably other Rho GTPases seriously compromises phagocyte function.     

Cytokines inSalmonella infection

Before the onset of specific immune response, the host defence against Salmonella infection is regulated by cytokines characteristic for immunity to intracellular bacteria. Cytokine response to non-typhoidal Salmonellae is described.     

Pneumocystis infection enhances antibody-mediated resistance to a subsequent influenza infection

In contrast to the detrimental outcomes most often associated with the resolution of coinfections, the model presented here involving a localized Pneumocystis infection of the lung, followed 2 wk later by an influenza virus infection, results in a significant beneficial outcome for the host. In the week following the influenza infection, immunocompetent coinfected animals exhibited an accelerated rate of virus clearance, an accelerated appearance of higher influenza-specific neutralizing Ab titers in their serum and bronchoalveolar lavage fluid (BALF), significantly reduced inflammatory cytokine levels in their BALF, and reduced levels of morbidity relative to animals infected only with influenza virus. The beneficial outcome observed in coinfected immunocompetent animals was dependent on the ongoing resolution of a viable Pneumocystis infection. No differences in viral clearance were detected between coinfected and influenza-only-infected muMT mice or likewise for SCID mice. The accelerated anti-influenza response did not appear to be associated with influenza-specific CD8 T cell-mediated responses or NK cell responses in the lung. Rather, the increased rate of viral clearance was due to the enhancement of the influenza-specific Ab response, which in turn was transiently dependent upon the resolution of the ongoing Pneumocystis infection.     

TRIMming Flavivirus infection

Tripartite motif (TRIM) proteins are novel players in antiviral innate immunity. In this issue of Cell Host & Microbe,Taylor et?al. (2011) discover the mechanism of action of TRIM79α and show that this interferon-induced protein restricts tick-borne flaviviruses by targeting the viral polymerase for degradation.