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Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism.

Hyper-virulent Streptococcus pneumoniae serotype 1 strains are endemic in Sub-Saharan Africa and frequently cause lethal meningitis outbreaks. It remains unknown whether genetic variation in serotype 1 strains modulates tropism into cerebrospinal fluid to cause central nervous system (CNS) infections, particularly meningitis. Here, we address this question through a large-scale linear mixed model genome-wide association study of 909 African pneumococcal serotype 1 isolates collected from CNS and non-CNS human samples. By controlling for host age, geography, and strain population structure, we …

A Masquerading Case of Cryptococcus neoformans.

Cryptococcus is a common infection in immunocompromised hosts. Ordinarily, Cryptococcus tends to have a strong tropism for the central nervous system (CNS). Other organs or systems of the body are less commonly involved. Here we describe a patient who had cutaneous tropism. The predominant presentation of this patient was painful thigh lesions. This case highlights several practical difficulties in identifying such infections, and also demonstrates the clinical utility of some of the commonly followed practices in infectious diseases and medicine.

Genomic Analysis of MSM Rectal Chlamydia trachomatis Isolates Identifies Predicted Tissue-Tropic Lineages Generated by Intraspecies Lateral Gene Transfer-Mediated Evolution.

Chlamydia trachomatis is an obligate intracellular bacterium that causes serious diseases in humans. Rectal infection and disease caused by … nome-wide association study was then used to identify genomic loci that were correlated with tissue tropism in a collection of serovar-matched male rectal and female cervical strains. The polymorphic membrane protein PmpE had the strongest correlation, and amino acid sequence alignments identified a set of PmpE variable regions (VRs) that were correlated …

Pathological modeling of TBEV infection reveals differential innate immune responses in human neurons and astrocytes that correlate with their susceptibility to infection.

BACKGROUND: Tick-borne encephalitis virus (TBEV) is a member of the Flaviviridae family, Flavivirus genus, which includes several important human pathogens. It is responsible for neurological symptoms that may cause permanent disability or death, and, from a medical point of view, is the major arbovirus in Central/Northern Europe and North-Eastern Asia. TBEV tropism is critical for neuropathogenesis, yet little is known about the molecular mechanisms that govern the susceptibility of human brain cells to the virus. In this study, we sought to establish and characterize a new in vitro model of …

Enhancing in vivo cell and tissue targeting by modulation of polymer nanoparticles and macrophage decoys.

The in vivo efficacy of polymeric nanoparticles (NPs) is dependent on their pharmacokinetics, including time in circulation and tissue tropism. Here we explore the structure-function relationships guiding physiological fate of a library of poly(amine-co-ester) (PACE) NPs with different compositions and surface properties. We find that circulation half-life as well as tissue and cell-type tropism is dependent on polymer chemistry, vehicle characteristics, dosing, and strategic co-administration of distribution modifiers, suggesting that physiological fate can be optimized by adjusting these par…

Phenotypic heterogeneity in a panel of infectious molecular human immunodeficiency virus type 1 clones derived from a single individual.

Previously, we and others have demonstrated a relation between the clinical course of human immunodeficiency virus type 1 (HIV-1) infection and biological properties of HIV-1 variants such as replication rate, syncytium-inducing (SI) capacity, and cytotropism. For the molecular analysis of the biological variability in these properties, we generated a panel of phenotypically distinct yet genetically highly homologous infectious molecular clones. These clones were derived from HIV-1 isolates, mostly recovered by direct clonal isolation, from a single individual in whom a transition from non-SI …

Pmp Справочники влияют на различные инфекционные возможности птичьего и млекопитающего хламидио-пситтаси Страинз.

Хламидио пситтачи является этиологическим агентом хламидиоза у птиц и может передаваться людям, вызывая серьезные системные заболевания. С. пситтаци заражает широкий круг носителей; штаммы изолированы не только от птиц, но и от млекопитающих, где, как представляется, они имеют ограниченный инфекционный и зоонотический потенциал. Сравнительный анализ хламидиальных геномов показал, что последовательности кодирования полиморфных мембранных белков (Pmps) являются весьма изменчивыми регионами. ППМ характеризуются как адгезины в C. trachomatis и C. пневмонии и являются иммунореактивными белками в не

Совпадение в аннотации оригинала
Chlamydia psittaci is the etiological agent of chlamydiosis in birds and can be transmitted to humans, causing severe systemic disease. C. p … ctive proteins in several Chlamydia species. Thus, Pmps are considered to be associated with tissue tropism and pathogenicity. C. psittaci harbors 21 Pmps. We hypothesize that the different infectious potential and host tropism of avian and mammalian C. psittaci strains is dependent on differences in their Pmp repertoires. In this study, we experimentally …

Chimeric Helper-Dependent Adenoviruses Transduce Retinal Ganglion Cells and Müller Cells in Human Retinal Explants.

Purpose: Despite numerous recent advances in retinal gene therapy using adeno-associated viruses (AAVs) as delivery vectors, there remains a crucial need to identify viral vectors with the ability to transduce specific retinal cell types and that have a larger carrying capacity than AAV. In this study, we evaluate the retinal tropism of 2 chimeric helper-dependent adenoviruses (HDAds), helper-dependent adenovirus serotype 5 (HDAd5)/3 and HDAd5/35, both ex vivo using human retinal explants and in vivo using rats. Methods: We transduced cultured human retinal explants with HDAd5/3 and HDAd5/35 c…

Human T-Cell Leukemia Virus Type 1 Envelope Protein: Post-Entry Roles in Viral Pathogenesis.

Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that is the causative infectious agent of adult T-cell leukemia/lymph … o, HTLV-1 primarily immortalizes or transforms CD4+ T-cells, while HTLV-2 displays a transformation tropism for CD8+ T-cells. This distinct tropism is recapitulated in infected people. Through comparative studies, the genetic determinant for this divergent tropism of HTLV-1/2 has been mapped to the viral envelope (Env). In this review, we explore the emer …

The unfolding palette of COVID-19 multisystemic syndrome and its neurological manifestations.

Although our current knowledge of the pathophysiology of COVID-19 is still fragmentary, the information so far accrued on the tropism and life cycle of its etiological agent SARS-CoV-2, together with the emerging clinical data, suffice to indicate that the severe acute pulmonary syndrome is the main, but not the only manifestation of COVID-19. Necropsy studies are increasingly revealing underlying endothelial vasculopathies in the form of micro-haemorrhages and micro-thrombi. Intertwined with defective antiviral responses, dysregulated coagulation mechanisms, abnormal hyper-inflammatory reacti…

Organs infected with Trypanosoma cruzi and DTU identification in the naturally infected rodent Octodon degus.

Chagas disease is a public health problem in America. Its parasite, Trypanosoma cruzi, presents different discrete typing units (DTUs), colonizes organs of mammalian hosts in chronic infections, and presents tropism for particular organs in experimental infections. We evaluated T. cruzi tropism towards organs on the naturally infected rodent Octodon degus, identifying the parasites' DTUs, by means of conventional PCR and hybridization. Almost all the analyzed organs presented T. cruzi. More than 42% of the tested oesophagus, skin, skeletal muscle, brain and intestine showed T. cruzi DNA. Other…

Anatomo-clinical and molecular description of liver neotropical echinococcosis caused by Echinococcus oligarthrus in human host.

Since humans rarely play the role as Echinococcus oligarthrus host, there is lack of knowledge about the complex infectious process. Only three cases have been reported to occur in humans in the neotropics until now. We present the anatomo-clinical and molecular findings describing a new case of infection by E. oligarthrus in a man. The muscular or subcutaneous tissues tropism described for this species in the previously reported cases was not present, but a liver tropism was observed. Additionally, the larval stage rostellar hooks morphometry differed from E. oligarthrus in the other human ca…

Infection and Replication of Influenza Virus at the Ocular Surface.

Although influenza viruses typically cause respiratory tract disease, some viruses, particularly those with an H7 hemagglutinin, have been isolated from the eyes of conjunctivitis cases. Previous work has shown that isolates of multiple subtypes from both ocular and respiratory infections are capable of replication in human ex vivo ocular tissues and corneal or conjunctival cell monolayers, leaving the determinants of ocular tropism unclear. Here, we evaluated the effect of several variables on tropism for ocular cells cultured in vitro and examined the potential effect of the tear film on vir…

Evaluation of Rift Valley fever vaccine candidates in pregnant rodent models.

BACKGROUND: Rift Valley fever virus (RVFV) causes significant disease in humans and livestock. Immunogenicity of candidate vaccines rMP-12 and RVax-1 show promise, but their placental tropism and potential effects on fetal outcomes remain incompletely understood, particularly across different animal models. Understanding species-specific placental replication is essential to optimize vaccine safety in pregnant populations. OBJECTIVE: To evaluate the placental tropism and fetal outcomes of RVFV candidate vaccines rMP-12 and RVax-1 in pregnant Sprague-Dawley (SD) rats and C57BL/6 mice. METHODS…

Engineering a streamlined virus-like particle for programmable tissue-specific gene delivery.

Transient gene delivery vehicles have emerged as crucial tools in biomedicine, among them, virus-like particles (VLPs) stand out for their unique characteristics, yet the limited tropisms hinder their widespread applications. VLPs have potential to broaden their targeting range through the acquisition of programmable tropisms, however, current retrovirus-based VLPs pose engineering challenges due to multiple viral proteins. Here, we streamline the VLP system by customizing a backbone utilizing positive-strand Semliki Forest Virus (SFV) for a programmable VLP vector, minimizing virus-derived co…

The eyes have it: influenza virus infection beyond the respiratory tract.

Avian and human influenza A viruses alike have shown a capacity to use the eye as a portal of entry and cause ocular disease in human beings. However, whereas influenza viruses generally represent a respiratory pathogen and only occasionally cause ocular complications, the H7 virus subtype stands alone in possessing an ocular tropism. Clarifying what confers such non-respiratory tropism to a respiratory virus will permit a greater ability to identify, treat, and prevent zoonotic human infection following ocular exposure to influenza viruses; especially those within the H7 subtype, which contin…

Allogeneic human neural stem cells for improved therapeutic delivery to peritoneal ovarian cancer.

BACKGROUND: Immortalized, clonal HB1.F3.CD 21 human neural stem/progenitor cells (NSCs), loaded with therapeutic cargo prior to intraperitoneal (IP) injection, have been shown to improve the delivery and efficacy of therapeutic agents in pre-clinical models of stage III ovarian cancer. In previous studies, the distribution and efficacy of the NSC-delivered cargo has been examined; however, the fate of the NSCs has not yet been explored. METHODS: To monitor NSC tropism, we used an unconventional method of quantifying endocytosed gold nanorods to overcome the weaknesses of existing cell-trackin…

Advances in endothelial cell targeting by AAV vectors.

Adeno-associated virus (AAV) vectors have become a cornerstone of in vivo gene delivery. However, although the endothelium is the first cellular interface encountered after systemic delivery, native AAV serotypes exhibit poor endothelial transduction, favoring hepatocytes, muscle cells and, neurons instead. This limitation represents a major barrier to gene therapies targeting cardiovascular, neurovascular, and inflammatory diseases. This review summarizes recent advances in redirecting AAV tropism toward endothelial cells (ECs) through genetic capsid engineering, peptide display, and non-gene…

Virotherapy of ovarian cancer with polymer-cloaked adenovirus retargeted to the epidermal growth factor receptor.

Adenovirus gene therapy for intraperitoneal (IP) cancer is limited in clinical trials by inefficient tumor cell transduction and development of peritoneal adhesions. We have shown previously that normal virus tropism can be ablated by physically shielding the virus surface with reactive hydrophilic polymers and that linkage of novel ligands enables virus "retargeting" through chosen receptors. To achieve tumor-selective infection, polymer-coated virus was retargeted using murine epidermal growth factor (mEGF). The resulting mEGF-polymer coated adenovirus lost its normal broad tropism and trans…

Enhancement of guinea pig cytomegalovirus infection by two endogenously expressed components of the pentameric glycoprotein complex in epithelial cells.

A better understanding of the mechanisms underlying cell tropisms and the efficiency of viral infection is critical for the development of vaccines and antiviral drugs for viral diseases. In this study, we worked on the entry mechanisms of guinea pig cytomegalovirus and found that endogenous expression of a combination of two components (GP131 and GP133) of the pentameric glycoprotein complex, which is required for non-fibroblast cell tropisms, enhanced viral infection more than 10-fold. In addition, D138A alteration in GP131 increased this enhancement by an additional 10-fold. Although differ…