Modulation of Synaptic Plasticity Genes Associated to DNA Damage in a Model of Huntington's Disease.

Huntington's disease (HD) is a disease characterized by the progressive degeneration of nerve cells in the brain. DNA damage has been implicated in many neurological disorders; however, the association between this damage and the impaired signaling related to neurodegeneration is still unclear. The transcription factor c-AMP-responsive element binding protein (CREB) has a relevant role in the neuronal plasticity process regulating the expression of several genes, including brain-derived neurotrophic factor (BDNF). Here we analyzed the direct link between DNA damage and the expression of genes involved in neuronal plasticity. The study was performed in model cell lines STHdhQ7 (wild type) and STHdhQ111 (HD model). Treatment with Etoposide (Eto) was used to induce double-strand breaks (DSBs) to evaluate the DNA damage response (DDR) and the expression of synaptic plasticity genes. Eto treatment induced phosphorylation of ATM (p-ATM) and H2AX (γH2AX), markers of DDR, in both cell lines. Interestingly, upon DNA damage, STHdhQ7 cells showed increased expression of activity-regulated cytoskeleton associated protein (Arc) and BDNF when compared to the HD cell line model. Additionally, Eto induced CREB activation with a differential localization of its co-activators in the cell types analyzed. These results suggest that DSBs impact differentially the gene expression patterns of plasticity genes in the normal cell line versus the HD model. This effect is mediated by the impaired localization of CREB-binding protein (CBP) and histone acetylation in the HD model. Our results highlight the role of epigenetics and DNA repair on HD and therefore we suggest that future studies should explore in depth the epigenetic landscape on neuronal pathologies with the goal to further understand molecular mechanisms and pinpoint therapeutic targets.

The Andes Orthohantavirus NSs Protein Antagonizes the Type I Interferon Response by Inhibiting MAVS Signaling.

The small messenger RNA (SmRNA) of the Andes orthohantavirus (ANDV), a rodent-borne member of the Hantaviridae family of viruses of the Bunyavirales order, encodes a multifunctional nucleocapsid (N) protein and for a nonstructural (NSs) protein of unknown function. We have previously shown the expression of the ANDV-NSs, but only in infected cell cultures. In this study, we extend our early findings by confirming the expression of the ANDV-NSs protein in the lungs of experimentally infected golden Syrian hamsters. Next, we show, using a virus-free system, that the ANDV-NSs protein antagonizes the type I interferon (IFN) induction pathway by suppressing signals downstream of the melanoma differentiation-associated protein 5 (MDA5) and the retinoic acid-inducible gene 1 (RIG-I) and upstream of TBK1. Consistent with this observation, the ANDV-NSs protein antagonized mitochondrial antiviral-signaling protein (MAVS)-induced IFN-ß, NF-κB, IFN-regulatory factor 3 (IRF3), and IFN-sensitive response element (ISRE) promoter activity. Results demonstrate that ANDV-NSs binds to MAVS in cells without disrupting the MAVS-TBK-1 interaction. However, in the presence of the ANDV-NSs ubiquitination of MAVS is reduced. In summary, this study provides evidence showing that the ANDV-NSs protein acts as an antagonist of the cellular innate immune system by suppressing MAVS downstream signaling by a yet not fully understand mechanism. Our findings reveal new insights into the molecular regulation of the hosts' innate immune response by the Andes orthohantavirus.IMPORTANCEAndes orthohantavirus (ANDV) is endemic in Argentina and Chile and is the primary etiological agent of hantavirus cardiopulmonary syndrome (HCPS) in South America. ANDV is distinguished from other hantaviruses by its unique ability to spread from person to person. In a previous report, we identified a novel ANDV protein, ANDV-NSs. Until now, ANDV-NSs had no known function. In this new study, we established that ANDV-NSs acts as an antagonist of cellular innate immunity, the first line of defense against invading pathogens, hindering the cellular antiviral response during infection. This study provides novel insights into the mechanisms used by ANDV to establish its infection.

Transcriptional analysis of flagellar and putative virulence genes of Arcobacter butzleri as an endocytobiont of Acanthamoeba castellanii.

Arcobacter butzleri is an emerging foodborne zoonotic pathogen that has been isolated from environmental water sources. This pathogen establishes in vitro endosymbiotic relationships with Acanthamoeba castellanii, a free-living amoeba found in environmental matrices such as soil and water. The principal aim of this study was to analyse the transcriptional pattern of flagellar (flaA-flaB-flgH-motA) and other putative virulence genes (ciaB-cadF-mviN-pldA) of A. butzleri during its interaction with A. castellanii by quantitative real-time PCR. The transcriptional analysis showed up-regulation of all genes analysed before A. butzleri became established as an endocytobiont of A. castellanii. In contrast, while A. butzleri remains an endocytobiont, a significant and sustained decrease in the transcription of all analysed genes was observed. Our findings suggest that A. butzleri requires a biphasic transcriptional pattern of flagellar and other putative virulence genes to establish an endosymbiotic relationship with A. castellanii.

Interleukin-3 Prevents Cellular Death Induced by Oxidative Stress in HEK293 Cells.

Interleukin-3 (IL-3) is a well-characterized growth factor in hematopoietic cells, but it is also expressed in other cell types with poorly described functions. Many studies have provided evidence that IL-3 plays an important role in cell survival. We have previously shown that IL-3 is able to increase glucose uptake in HEK293 cells, suggesting that this factor requires sustained glucose metabolism to promote cell survival. In this study, we demonstrate that IL-3 contributes to cell survival under oxidative stress, a prominent feature in the pathophysiology of cancer, diabetes, and neurodegenerative diseases, as well as in the aging process. Our results suggest a molecular mechanism that involves signaling pathways mediated by PI-3k/Akt and Erk. Altogether, these findings show an important role for IL-3 in supporting the viability of non-hematopoietic systems. J. Cell. Biochem. 118: 1330-1340, 2017. © 2016 Wiley Periodicals, Inc.

The Effect of Resveratrol on Cell Viability in the Burkitt's Lymphoma Cell Line Ramos.

Resveratrol is a polyphenolic natural compound produced by a variety of crops. Currently, resveratrol is considered a multi-target anti-cancer agent with pleiotropic activity, including the ability to prevent the proliferation of malignant cells by inhibiting angiogenesis and curtailing invasive and metastatic factors in many cancer models. However, the molecular mechanisms mediating resveratrol-specific effects on lymphoma cells remain unknown. To begin tackling this question, we treated the Burkitt's lymphoma cell line Ramos with resveratrol and assessed cell survival and gene expression. Our results suggest that resveratrol shows a significant anti-proliferative and pro-apoptotic activity on Ramos cells, inducing the DNA damage response, DNA repairing, and modulating the expression of several genes that regulate the apoptotic process and their proliferative activity.

Mechanisms associated with phagocytosis of Arcobacter butzleri by Acanthamoeba castellanii.

Acanthamoeba castellanii is a free-living amoeba widely found in environmental matrices such as soil and water. Arcobacter butzleri is an emerging potential zoonotic pathogen that can be isolated from environmental water sources, where they can establish endosymbiotic relationships with amoebas. The aim of this study was to describe the implication of mannose-binding proteins and membrane-associated receptors of glucose and galactose present in the amoebic membrane, during the attachment of Arcobacter butzleri by blocking with different saccharides. Another objective was to describe the signaling pathways involved in phagocytosis of these bacteria using specific inhibitors and analyze the implication of phagolysosome formation on the survival of Arcobacter butzleri inside the amoeba. We infer that the attachment of Arcobacter butzleri to the amoeba is a process which involves the participation of mannose-binding proteins and membrane-associated receptors of glucose and galactose present in the amoeba. We also demonstrated an active role of protozoan actin polymerization in the phagocytosis of Arcobacter butzleri and a critical involvement of PI3K and RhoA pathways. Further, we demonstrated that the tyrosine kinase-induced actin polymerization signal is essential in Acanthamoeba-mediated bacterial uptake. Through phagolysosomal formation analysis, we conclude that the survival of Arcobacter butzleri inside the amoeba could be related with the ability to remain inside vacuoles not fused with lysosomes, or with the ability to retard the fusion between these structures. All these results help the understanding of the bacterial uptake mechanisms used by Acanthamoeba castellanii and contribute to evidence of the survival mechanisms of Arcobacter butzleri.

Herpes simplex virus type 1 induces simultaneous activation of Toll-like receptors 2 and 4 and expression of the endogenous ligand serum amyloid A in astrocytes.

Herpes simplex virus type 1 (HSV-1) is the most common pathogenic cause of sporadic acute encephalitis and it produces latent persistent infection lifelong in infected individuals. Brain inflammation is associated with activation of glial cells, which can detect pathogen-associated molecular patterns (PAMPs) through a variety of pattern-recognition receptors (PRR), including Toll-like receptors (TLRs). In this study, we evaluated the expression and activation of TLR2, TLR3, and TLR4 in HSV-1-infected astrocyte and neuronal primary cultures. Our results showed a clear induction in TLR2 and TLR4 expression in astrocytes as early as 1 h after HSV-1 infection, whereas no significant change was observed in neurons. In addition, infected astrocytes showed increased levels of interferon regulatory factors IRF3 and IRF7, interferon ß (INFß), interleukin 6 (IL6), and serum amyloid A (SAA3) transcripts, as well as phospho-IRF3 protein. These effects seemed to be dependent on viral replication since previous treatment of the cells with acyclovir resulted in low levels of TLRs expression and activation even after 4 h post-infection. These results suggest that reactivation of HSV-1 at the central nervous system (CNS) would likely induce and activate TLR2 and TLR4 receptors directly through interaction of astrocytes with the pathogen and also indirectly by endogenous ligands produced locally, such as serum amyloid protein, potentiating the neuroinflammatory response.

Subtyping of Chilean Methicillin-Resistant Staphylococcus aureus strains carrying the staphylococcal cassette chromosome mec type I.

The cassette chromosome mec (SCCmec) present in methicillin-resistant Staphylococcus aureus (MRSA) has two essential components, the ccr gene complex and the mec gene complex. Additionally, SCCmec has non-essential components called J regions which are used for MRSA subtyping. This study was performed to determine subtypes MRSA strains carrying SCCmec type I based on polymorphism of regions located downstream of the mecA gene. A total of 98 MRSA strains carrying SCCmec type I isolated from patients hospitalized at the County Hospital of Valdivia (Chile) between May 2007 and May 2008, were analyzed by multiplex PCR designed to amplify the mecA gene and 7 DNA hypervariable regions located around the mecA gene. MRSA strains were classified into seventeen genotypes accordingly to amplification patterns of DNA hypervariable regions. Five genotypes showed amplification patterns previously described. The remaining twelve genotypes showed new amplification patterns. Genotypes 18 and Genotype 19 were the most frequently detected. Regions HVR, Ins117 and pI258 stand out as being present in more than 60% of tested isolates. The acquisition of hypervariable regions by MRSA is a continuous horizontal transfer process through which the SCCmec have been preserved intact, or even may give rise to new types and subtypes of SCCmec. Therefore it is possible to infer that most MRSA strains isolated at the County Hospital of Valdivia (Chile) were originated from two local clones which correspond to Genotype 18 and Genotype 19.

Prevalence of human T-cell lymphotropic virus type 1 and 2 among patients with malignant hematological diseases in south Chile.

Human T-cell lymphotropic virus type 1 and 2 (HTLV-1/2) are oncogenic retroviruses linked etiologically to human diseases. In Chile, these viruses have been studied in ethnic populations, or patients diagnosed clinically with HTLV-1 associated myelopathy/tropical spastic paraparesis, but have not been studied in patients with malignant hematological diseases. The aim of this study was to determine the seroprevalence and viral prevalence of HTLV-1/2 among patients with malignant hematological diseases. Eighty-eight patients with malignant hematological diseases were tested by enzyme-linked immunosorbent assay (ELISA) for IgG anti-HTLV-1/2 and nested-PCR for the tax gene. The seroprevalence by ELISA was 3.4% and the viral prevalence by nested-PCR tax was 18.2%. HTLV-1 was found in 17% and HTLV-2 in 1% of the patients tested. HTLV-1/2 was found in 17.4% of patients with non-Hodgkin's lymphomas, 28.6% of patients with Hodgkin's lymphomas, 80% of patients with chronic lymphocytic leukemia, 11.4% of patients with acute lymphoblastic leukemia, and 22.2% of patients with acute myeloid leukemia. A high prevalence of HTLV-1/2 was found in patients with malignant hematological diseases. A high proportion of patients were seronegative to HTLV-1/2 infection, similar to other HTLV-1/2 associated disorders. Because 50% of patients positive for HTLV-1/2 were below 30 years old, it is suggested that vertical transmission could have played an important role in these patients.

[Herpes simplex virus type 1 as risk factor associated to Alzheimer disease]. / Herpes simplex virus tipo 1 como factor de riesgo asociado con la enfermedad de Alzheimer.

Herpes simplex virus type 1 (HSV-1) is ubiquitous, neurotropic, and the most common pathogenic cause of sporadic acute encephalitis in humans. Herpes simplex encephalitis is associated with a high mortality rate and significant neurological, neuropsychological, and neurobehavioral sequels. HSV-1 infects limbic system structures in the central nervous system (CNS), and has been suggested as an environmental risk factor for Alzheimer's disease. The possibility that HSV-1 reactivates in CNS neurons causing chronic progressive damage at cellular level and altering the neuronal functionality has not been thoroughly investigated. Currently it is ignored if recurrent reactivation of HSV-1 in asymptomatic patients involves some risk of progressive deterioration of the CNS functions caused, in example, by a neuroinflammatory response against the virus or by direct toxicity of the pathogen on neurons. Therefore, studies regarding the routes of dissemination of HSV-1 from the peripheral ganglions to the CNS, as well as the possible cellular and molecular mechanisms implied in generating neuronal damage during latent and productive infection, are of much relevance.

Isolation of Helicobacter pylori in gastric mucosa and susceptibility to five antimicrobial drugs in Southern chile.

Helicobacter pylori colonizes more than 50% of the world population thus, it is considered an important cause of gastric cancer. The aim of this study was to determine the isolation frequency of H. pylori in Southern Chile from patients with symptomatology compatible with gastritis or gastric ulcer and to correlate these findings with demographic parameters of infected patients and the susceptibility profiles of the isolated strains to the antimicrobial drugs used in the eradication treatments. A total of 240 patients were enrolled in the study. Each gastric biopsy was homogenized and seeded onto blood agar plates containing a selective antibiotics mixture (DENT supplement). Plates were incubated at 37° C in a microaerophilic environment for five days. The susceptibility profiles to amoxicillin, ciprofloxacin, clarithromycin, tetracycline and metronidazole were determined using the E-test method. H. pylori was isolated from 99 patients (41.3%) with slightly higher frequency in female (42% positive cultures) than male (40.2% positive cultures). With regard to age and educational level, the highest isolation frequencies were obtained in patients between 21-30 (55%) and 41-50 (52.6%) years old, and patients with secondary (43.9%) and university (46.2%) educational levels. Nineteen (21.6%) strains showed resistance to at least one antimicrobial drug. Tetracycline was the most active antimicrobial in vitro, whereas metronidazole was the less active. One strain (5.3%) showed resistance to amoxicillin, clarithomycin and metronidazole, simultaneously.

Genetic diversity of Hepatozoon spp. in rodents from Chile.

This study aimed to investigate the genetic diversity of Hepatozoon spp. in rodents from Valdivia, Chile. A total of 74 rodents (synanthropic n=38; wild n=36) were trapped in Valdivia. We performed conventional PCR assays for Apicomplexa organisms targeting two overlapping 18S rDNA gene fragments (600 bp and 900 bp) followed by sequencing of selected amplicons. Hepatozoon spp. occurrence was 82.43% (61/74). Twelve sequences obtained from the 600 bp and ten from the 900 bp 18S rDNA fragments were identified as Hepatozoon sp. Six sequences obtained from 18S rDNA-based overlapping PCR protocols were used for concatenated (1,400 bp) phylogenetic, haplotype and distance analyses. Hepatozoon spp. 18S rDNA concatenated sequences from the present study were detected in Oligoryzomys longicaudatus, Rattus norvegicus, Mus musculus, and Abrothrix longipilis grouped with Hepatozoon species earlier described in rodents and reptiles from Chile and Brazil. Nucleotide polymorphism of the six 18S rDNA sequences (1,400 bp) from this study, and other Chilean sequences from rodents and rodent's ticks, showed high diversity with a total of nine Chilean haplotypes. Three haplotypes from Valdivia were identified for the first time in this study, suggesting the circulation of novel haplotypes in rodents from southern Chile.

Herpes Simplex Virus Type 1 Neuronal Infection Triggers the Disassembly of Key Structural Components of Dendritic Spines.

Herpes simplex virus type 1 (HSV-1) is a widespread neurotropic virus. Primary infection of HSV-1 in facial epithelium leads to retrograde axonal transport to the central nervous system (CNS) where it establishes latency. Under stressful conditions, the virus reactivates, and new progeny are transported anterogradely to the primary site of infection. During the late stages of neuronal infection, axonal damage can occur, however, the impact of HSV-1 infection on the morphology and functional integrity of neuronal dendrites during the early stages of infection is unknown. We previously demonstrated that acute HSV-1 infection in neuronal cell lines selectively enhances Arc protein expression - a major regulator of long-term synaptic plasticity and memory consolidation, known for being a protein-interaction hub in the postsynaptic dendritic compartment. Thus, HSV-1 induced Arc expression may alter the functionality of infected neurons and negatively impact dendritic spine dynamics. In this study we demonstrated that HSV-1 infection induces structural disassembly and functional deregulation in cultured cortical neurons, an altered glutamate response, Arc accumulation within the somata, and decreased expression of spine scaffolding-like proteins such as PSD-95, Drebrin and CaMKIIß. However, whether these alterations are specific to the HSV-1 infection mechanism or reflect a secondary neurodegenerative process remains to be determined.

Prevalence of Epstein-Barr virus associated with nasal lymphoma in patients attending the regional hospital of Valdivia, Chile, between 1987 and 2005.

Epstein-Barr virus (EBV) is a ubiquitous herpes virus with a widespread infection in the world's adult population. EBV has been associated with human malignancies, mainly the nasal type NK/T cell lymphoma. The disease is more frequent in Asian than in Western countries. However, there are few studies from Latin American countries. The aim of this study was to determine the prevalence of EBV in patients with nasal lymphomas diagnosed in the Regional Hospital of Valdivia, southern Chile, during 1987-2005. Immunohistochemistry was done on paraffin sections using anti-CD3epsilon, anti-CD20, and anti-CD56. The presence of small ribonucleic acids (RNAs) of EBV was detected in paraffin sections by in situ hybridization using oligonucleotides targeting EBV-encoded small RNAs. The present study revealed a prevalence of 27.7% of Hodgkin's lymphomas and 72.3% of non-Hodgkin's lymphomas. From the latter group, there was a prevalence of 2.9% (10 cases) of nasal lymphoma. From these 10 cases, 6 (60%) were NK/T cell lymphomas, nasal type; 1 case (10%) was a T-cell phenotype; and 3 cases (30%) were B-cell phenotype. The prevalence was higher than reports from Western countries, but lower than the reports from Asian countries. These results agreed with previous reports suggesting that EBV is strongly associated with T lymphomas. This study contributes new epidemiological data on EBV in Chile.

Seroprevalence of human T-cell lymphotropic virus type 1 and 2 in blood donors from the regional hospital of Valdivia, Chile.

It is estimated that 15-20 millions of people are infected with human T-cell lymphotropic virus 1/2 (HTLV-1/2) worldwide, and 20-30% of them are Latin Americans. The seroprevalence rates vary according to geographic area, socio-demographic composition and individual risk behaviors. The impact of HTLV-1-associated diseases on the community, as well as the increasing concerns about blood transfusion safety due to infectious transmitted agents, has required mandatory screening assays of blood donors as an effective preventive strategy in HTLV-1 transmission. The aim of this study was to estimate the seroprevalence of HTLV-1/2 in blood donors from Valdivia, southern Chile during the first year of mandatory screening of HTLV by Chilean government. Blood samples were collected from blood donors between May 2009 and 2010 at the Regional Hospital of Valdivia, Chile. Serum samples were screened for antibodies against HTLV-1/2 by enzyme-linked immunosorbent assay MUREX HTLV I + II Abbott. Among 6,237 samples tested by serological assay, 28 samples were reactive; nevertheless, confirmatory techniques indicate that only 15 samples were positive to HTLV-1. Our study shows HTLV-1 seroprevalence of 0.24%, indicating a similar seroprevalence associated with blood donors than previous reports for our country.

Involvement of Kallikrein-Related Peptidases in Nervous System Disorders.

Kallikrein-related peptidases (KLKs) are a family of serine proteases that when dysregulated may contribute to neuroinflammation and neurodegeneration. In the present review article, we describe what is known about their physiological and pathological roles with an emphasis on KLK6 and KLK8, two KLKs that are highly expressed in the adult central nervous system (CNS). Altered expression and activity of KLK6 have been linked to brain physiology and the development of multiple sclerosis. On the other hand, altered levels of KLK6 in the brain and serum of people affected by Alzheimer's disease and Parkinson's disease have been documented, pointing out to its function in amyloid metabolism and development of synucleinopathies. People who have structural genetic variants of KLK8 can suffer mental illnesses such as intellectual and learning disabilities, seizures, and autism. Increased expression of KLK8 has also been implicated in schizophrenia, bipolar disorder, and depression. Also, we discuss the possible link that exists between KLKs activity and certain viral infections that can affect the nervous system. Although little is known about the exact mechanisms that mediate KLKs function and their participation in neuroinflammatory and neurodegenerative disorders will open a new field to develop novel therapies to modulate their levels and/or activity and their harmful effects on the CNS.

Molecular survey of Bartonella spp. in rodents and fleas from Chile.

The aim of this study was to molecularly survey Bartonella spp. in rodents from the Valdivia Province, Southern Chile and from wild black rat-fleas in Guafo Island, Chilean Patagonia. Thrity-three spleens from synanthropic (Mus musculus, Rattus novergicus and Rattus rattus) and wild (Abrothrix longipilis, Oligoryzomys longicaudatus, Abrothrix sp.) rodents from Valdivia and 39 fleas/flea-pools (Plocopsylla sp. and Nosopsyllus sp.) from R. rattus in Guafo Island were obtained. All samples were screened by high-resolution melting (HRM) real-time PCR for Bartonella ITS locus (190 bp). ITS-Positive samples were further analyzed for two HRM real-time PCR assays targeting Bartonella rpoB (191 bp) and gltA (340 bp) gene fragments. All positive ITS, gltA and rpoB real-time PCR products were purified and sequenced. Bayesian inference trees were built for the gltA and rpoB gene fragments. Bartonella-ITS DNA was detected in 36.3% (12/33) [95% CI (22-53%)] of the tested rodents from Valdivia, being identified in all but O. longicaudatus rodent species captured in this study. ITS DNA was detected in 28% (11/39) [95% CI (16-43%)] of fleas/flea-pools from Guafo Island and identified in both Plocopsylla and Nosopsyllus genera. Sequencing and phylogenic analyses targeting three loci of Bartonella spp. allowed the identification of five genotypes in rodents from Southern Chile, potentially belonging to three different Bartonella spp. Those included Bartonella tribocorum identified from R. rattus, Bartonella rochalimae detected from Abrothix sp., and one novel genotype from uncharacterized Bartonella sp. identified in M. musculus, R. norvegicus, A. longipilis, and Abothrix sp., related to strains previously isolated in Phyllotis sp. from Peru. Additionally, two genotypes of B. tribocorum were identified in fleas from Guafo. In a nutshell, highly diverse and potentially zoonotic Bartonella spp. are described for the first time in wild and synanthropic rodents from Chile, and B. tribocorum was detected in wild back rat fleas from Guafo Island.

Molecular Survey and Genetic Diversity of Hemoplasmas in Rodents from Chile.

Even though hemotrophic mycoplasma (hemoplasma) infections are well documented in a wide variety of hosts worldwide, there is a gap in the knowledge aobut hemoplasmas in rodents. This study aimed to molecularly survey and investigate the genetic diversity of hemoplasmas in rodents from Chile. Synanthropic and wild rodents (n = 74) were captured in the southern province of Valdivia (Corral, Valdivia, Riñihue, and Reumén localities). Spleen samples were submitted to a conventional PCR for hemotrophic Mycoplasma spp. targeting the 16S rRNA gene (800 bp), followed by sequencing, phylogenetic, and genetic diversity analyses. The overall occurrence of hemotrophic mycoplasmas in rodents from Valdivia was 24.5% (18/74) [95% CI (14.5; 34.1)]. Hemoplasmas were detected in Mus musculus (1/4), Rattus norvegicus (1/16), Abrothrix longipilis (7/13), A. olivaceo (6/8), and Oligoryzomys longicaudatus (3/10). The nucleotide polymorphism analysis of the targeted 16S rRNA region showed low diversity, with two genotypes and a high identity to the variants detected in wild rodents from Brazil. Hemoplasmas are described for the first time in rodents from Chile with a moderate occurrence and low 16S rDNA genetic diversity within the sampled rodent population. The detected hemoplasma genotypes were specific to rodents and were not shared with other mammals.

Immunocytochemical and Ultrastructural Evidence Supporting That Andes Hantavirus (ANDV) Is Transmitted Person-to-Person Through the Respiratory and/or Salivary Pathways.

In South America Andes hantavirus (ANDV) is hosted by the rodent Oligoryzomys longicaudatus (also known as pygmy rice rat). In humans, ANDV causes Hantavirus Pulmonary Syndrome (HPS), with a fatality rate of about 40%. Epidemiologic and molecular evidence has shown that ANDV can be transmitted from person to person. Sin Nombre hantavirus, occurring in North America, and ANDV are genetically related, and both cause HPS with similar clinical evolution and mortality rate. However, only ANDV is transmitted from person to person. A recent hantavirus outbreak in a small village in Southern Argentine, with 29 HPS cases and 11 deaths has brought to mind that person-to-person transmission continues to be a public health emergency. The present investigation was aimed to understand how does ANDV actually spread between persons. Tissue samples of lung and salivary glands from infected Oligoryzomys longicaudatus and lethal cases of human HPS were investigated by bright field immunocytochemistry, multichannel immunofluorescence, and transmission electron microscopy. The findings are consistent with ANDV infection and replication in the lung alveolar epithelium and macrophages, and in the secretory cells of the submandibular salivary glands. In the lung of infected Oligoryzomys longicaudatus and human cases HPS, the bulk of immunoreactive hantavirus antigens was localized in epithelial cells of the alveolar walls and macrophages. The ultrastructural study supports that in the lung of HPS patients the virus replicates in the alveolar epithelial cells with virus particles being discharged into the alveolar lumen. Virus-like particles were seen within vacuoles of the lung macrophages. Considering that these macrophages can reach the conductive segments of the airways, their expectoration becomes a deadly bullet for ANDV transmission. In the submandibular glands of infected rodents and HPS cases, ANDV antigens were in capillary endothelium, the secretory cells and filling the lumen of the excretory pathway. It is proposed that in patients with HPS caused by ANDV the alveolar epithelium and macrophages would be the gate for the airway spreading of the virus, while the salivary glands are a target for virus replication and an exit pathway through saliva.

Neuronal cytoskeletal dynamic modification and neurodegeneration induced by infection with herpes simplex virus type 1.

Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) belong to the family Herpesviridae, the subfamily Alphaherpesvirinae, and the genus Simplexvirus. They are ubiquitous, neurotropic, and the most common pathogenic cause of sporadic acute encephalitis in humans. Herpes simplex encephalitis (HSE) is associated with a high mortality rate and significant neurological, neuropsychological, and neurobehavioral sequelae, which afflict patients for life. HSV-1 has been suggested as an environmental risk factor for Alzheimer's disease. However, the mechanisms involved in HSV-1 infection that may trigger the neurodegenerative process are still unknown. In general, HSV-1 induced cytoskeletal alterations reported to date involve the overall disruption of one or more elements of the cytoskeleton in cell lines. Axonal injury has recently attracted attention as a key predictor for the outcome of a number of brain disorders. Here we show that infection of mice neuronal cultures with HSV-1 result in marked neurite damage and neuronal death. Furthermore, in this in vitro model of infection, neurons manifested considerable alterations in microtubule dynamics and tau hyperphosphorylation. These results suggest a possible link between HSV-1 infection and neuronal cytoskeletal disruption.