Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque

High levels of HIV-1 replication during the chronic phase of infection usually correlate with rapid progression to severe immunodeficiency. However, a minority of highly viremic individuals remains asymptomatic and maintains high CD4⁺ T cell counts. This tolerant profile is poorly understood and reminiscent of the widely studied nonprogressive disease model of SIV infection in natural hosts. Here, we identify transcriptome differences between rapid progressors (RPs) and viremic nonprogressors (VNPs) and highlight several genes relevant for the understanding of HIV-1-induced immunosuppression. RPs were characterized by a specific transcriptome profile of CD4⁺ and CD8⁺ T cells similar to that observed in pathogenic SIV-infected rhesus macaques. In contrast, VNPs exhibited lower expression of interferon-stimulated genes and shared a common gene regulation profile with nonpathogenic SIV-infected sooty mangabeys. A short list of genes associated with VNP, including CASP1, CD38, LAG3, TNFSF13B, SOCS1, and EEF1D, showed significant correlation with time to disease progression when evaluated in an independent set of CD4⁺ T cell expression data. This work characterizes 2 minimally studied clinical patterns of progression to AIDS, whose analysis may inform our understanding of HIV pathogenesis.

Chemotaxis of T-cells after infection of human choroid plexus papilloma cells with Echovirus 30 in an in vitro model of the blood-cerebrospinal fluid barrier

Enterovirus is the most common pathogen causing viral meningitis especially in children. Besides the blood-brain barrier (BBB) the choroid plexus, which forms the blood-cerebrospinal-fluid (CSF) barrier (BCSFB), was shown to be involved in the pathogenesis of enteroviral meningitis. In a human in vitro model of the BCSFB consisting of human choroid plexus papilloma cells (HIBCPP), the permissiveness of plexus epithelial cells for Echovirus 30 (EV30) was analyzed by immunoblotting and quantitative real-time PCR (Q-PCR). HIBCPP could be directly infected by EV30 from the apical as well as from the physiological relevant basolateral side. During an infection period of 5h no alterations of barrier function and cell viability could be observed. Analysis of the cytokine/chemokine-profile following enteroviral infection with a cytometric bead array (CBA) and Q-PCR revealed an enhanced secretion of PanGRO (CXCL1, CXCL2 and CXCL3), IL8 and CCL5. Q-PCR showed a significant upregulation of CXCL1, CXCL2 and CXCL3 in a time dependant manner. However, there was only a minor effect of HIBCPP-infection with EV30 on transepithelial T lymphocyte migration with or without the chemoattractant CXCL12. Moreover, CXCL3 did not significantly enhance T cell migrations. Therefore additional factors must be involved for the in vivo reported enhanced T cell migration into the CNS in the context of enteroviral meningitis. As HIBCPP are permissive for infection with EV30, they constitute a valuable human in vitro model to study viral infection at the BCSFB.

Infection with human herpesvirus 8 and transplant-associated gammopathy

BACKGROUND: The role of human herpesvirus (HHV)-8 in the pathogenesis of multiple myeloma and its pre-malignant state of monoclonal gammopathy is unclear. HHV-8 is transmitted by organ transplantation, representing a unique model with which to investigate primary HHV-8 infection. METHODS: The authors studied the incidence of clonal gammopathy in renal transplant recipients and correlated it with previous and recent HHV-8 infection. RESULTS: Clonal gammopathy was observed in 31 of 162 (19%) HHV-8-seronegative patients, in 5 of 17 (29%) HHV-8-seropositive patients, and in 9 of 24 (38%) HHV-8 seroconverters within 5 years after transplantation. Gammopathy was often transient, and no progression to myeloma was observed. Two patients with persistent gammopathy developed B-cell lymphoma. In a logistic regression model, HHV-8 serostatus of the graft recipient was significantly associated with subsequent development of gammopathy, with a relative risk (RR) of 1.9 and a 95% confidence interval (CI) of 0.5 to 6.4 for an HHV-8-seropositive recipient and an RR of 2.9 and a 95% CI of 1.01 to 8.0 for seroconverters as compared with baseline (HHV-8 seronegative). Other significant variables were cytomegalovirus (CMV) serostatus and the intensity of immunosuppression (RR of 10.4 and 95% CI of 2.6-41.7 for a CMV-negative recipient with a CMV-positive donor vs. a CMV-negative recipient with a CMV-negative donor and RR of 17.6 and 95% CI of 2.0-150.8 if OKT3 was used vs. no use of antilymphocytic substances). CONCLUSIONS: Transplant recipients with HHV-8 infection are more likely to develop clonal gammopathy. However, this risk is much lower than the risk conferred by CMV infection and antilymphocytic therapy, arguing against a major role of HHV-8 infection in the pathogenesis of clonal plasma cell proliferation.

HIV infection disrupts the sympatric host-pathogen relationship in human tuberculosis

The phylogeographic population structure of Mycobacterium tuberculosis suggests local adaptation to sympatric human populations. We hypothesized that HIV infection, which induces immunodeficiency, will alter the sympatric relationship between M. tuberculosis and its human host. To test this hypothesis, we performed a nine-year nation-wide molecular-epidemiological study of HIV-infected and HIV-negative patients with tuberculosis (TB) between 2000 and 2008 in Switzerland. We analyzed 518 TB patients of whom 112 (21.6%) were HIV-infected and 233 (45.0%) were born in Europe. We found that among European-born TB patients, recent transmission was more likely to occur in sympatric compared to allopatric host-pathogen combinations (adjusted odds ratio [OR] 7.5, 95% confidence interval [95% CI] 1.21-infinity, p = 0.03). HIV infection was significantly associated with TB caused by an allopatric (as opposed to sympatric) M. tuberculosis lineage (OR 7.0, 95% CI 2.5-19.1, p<0.0001). This association remained when adjusting for frequent travelling, contact with foreigners, age, sex, and country of birth (adjusted OR 5.6, 95% CI 1.5-20.8, p = 0.01). Moreover, it became stronger with greater immunosuppression as defined by CD4 T-cell depletion and was not the result of increased social mixing in HIV-infected patients. Our observation was replicated in a second independent panel of 440 M. tuberculosis strains collected during a population-based study in the Canton of Bern between 1991 and 2011. In summary, these findings support a model for TB in which the stable relationship between the human host and its locally adapted M. tuberculosis is disrupted by HIV infection.

Differences in primary sites of infection between zoonotic and human tuberculosis: results from a worldwide systematic review.

Tuberculosis (TB) is one of the most devastating infectious diseases worldwide. Whilst global burden estimates for M. tuberculosis infection (MtTB) are well established, accurate data on the contribution of zoonotic TB (zTB) caused by M. bovis or M. caprae to human TB are scarce. The association of M. bovis infection with extrapulmonary tuberculosis has been suggested repeatedly, though there is little scientific evidence available to support this relationship. The present study aimed to determine globally the occurrence of extrapulmonary TB and the primary site (i.e. primary body location affected) of zTB in comparison with MtTB, based on previously published reports. A systematic literature review was conducted in 32 different bibliographic databases, selecting reports on zTB written in English, French, German, Spanish or Portuguese. Data from 27 reports from Africa, America, Europe and the Western Pacific Region were extracted for analyses. Low income countries, in Africa and South-East Asia, were highly underrepresented in the dataset. The median proportion of extrapulmonary TB cases was significantly increased among zTB in comparison with data from registries of Europe and USA, reporting mainly MtTB cases (47% versus 22% in Europe, 73% versus 30% in the USA). These findings were confirmed by analyses of eight studies reporting on the proportions of extrapulmonary TB in comparable populations of zTB and MtTB cases (median 63% versus 22%). Also, disparities of primary sites of extrapulmonary TB between zTB and MtTB were detected. Our findings, based on global data, confirm the widely suggested association between zTB and extrapulmonary disease. Different disability weights for zTB and MtTB should be considered and we recommend separate burden estimates for the two diseases.

[Nocardia cyriacigeorgici: First report of invasive human infection]

BACKGROUND Diagnostic laboratories increasingly offer bacterial identification to the species level. The 17 nocardia species known to date differ in their clinical presentation, antibiotic resistance patterns and geographic distribution. The discovery of a new species with pathogenicity for humans calls for the characterization of its clinical and epidemiological properties. PATIENTS AND METHODS Nocardia isolated from multifocal brain abscesses of an immunocompromised patient were further identified by the analysis of their cellular fatty acids and sequencing of the 16S ribosomal DNA. Quantitative antibiotic resistance testing was performed with E-tests. RESULTS The 16S ribosomal DNA analysis showed a 99 % homology to Nocardia cyriacigeorgici. This is the first report of this species as an invasive human pathogen. N. cyriacigeorgici was found susceptible for meropenem, amikacin, ceftriaxon and cotrimoxazole. The combination of surgical drainage and antibiotic treatment for 13 months was curative. CONCLUSIONS N. cyriacigeorgici has the potential to cause invasive infections at least in immunocompromised patients. Comparing clinical and in vitro characteristics with N. asteroides, the main causative agent of nocardial infections in Europe, we found no clinically relevant differences.

HIV and human herpesvirus 8 co-infection across the globe: Systematic review and meta-analysis.

HIV-infection is an important risk factor for developing Kaposi sarcoma (KS), but it is unclear whether HIV-positive persons are also at increased risk of co-infection with human herpesvirus 8 (HHV-8), the infectious cause of KS. We systematically searched literature up to December 2012 and included studies reporting HHV-8 seroprevalence for HIV-positive and HIV-negative persons. We used random-effects meta-analysis to combine odds ratios (ORs) of the association between HIV and HHV-8 seropositivity and conducted random-effects meta-regression to identify sources of heterogeneity. We included 93 studies with 58,357 participants from 32 countries in sub-Saharan Africa, North and South America, Europe, Asia, and Australia. Overall, HIV-positive persons were more likely to be HHV-8 seropositive than HIV-negative persons (OR 1.99, 95% confidence interval [CI] 1.70-2.34) with considerable heterogeneity among studies (I(2) 84%). The association was strongest in men who have sex with men (MSM, OR 3.95, 95% CI 2.92-5.35), patients with hemophilia (OR 3.11, 95% CI 1.19-8.11), and children (OR 2.45, 95% CI 1.58-3.81), but weaker in heterosexuals who engage in low-risk (OR 1.42, 95% CI 1.16-1.74) or high-risk sexual behavior (OR 1.66, 95% CI 1.27-2.17), persons who inject drugs (OR 1.66, 95% CI 1.28-2.14), and pregnant women (OR 1.68, 95% CI 1.15-2.47), p value for interaction <0.001. In conclusion, HIV-infection was associated with an increased HHV-8 seroprevalence in all population groups examined. A better understanding of HHV-8 transmission in different age and behavioral groups is needed to develop strategies to prevent HHV-8 transmission.

Absence of Active Hepatitis C Virus Infection in Human Immunodeficiency Virus Clinics in Zambia and Mozambique.

Few studies have evaluated the prevalence of replicating hepatitis C virus (HCV) infection in sub-Saharan Africa. Among 1812 individuals infected with human immunodeficiency virus, no patient in rural Mozambique and 4 patients in urban Zambia were positive for anti-HCV antibodies. Of these, none had confirmed HCV replication.

Listeria monocytogenes infection in ruminants: Is there a link to the environment, food and human health? A review.

Listeria (L.) monocytogenes is widely distributed in the environment, but also has the ability to cause serious invasive disease in ruminants and humans. This review provides an overview of listeriosis in ruminants and discusses our insufficient understanding of reservoirs and possible cycling ofL. monocytogenes between animal and human hosts, food and the environment. It indicates gaps in our knowledge of the role of genetic subtypes in L. monocytogenes ecology and virulence as well as risk factors, in vivo diagnostics and pathogenesis of listeriosis in ruminants. Filling these gaps will contribute to improving the control of L. monocytogenes and enhancing disease prevention. As the prevalence of listeriosis in ruminants in Switzerland is likely to be underestimated, propositions concerning improvement options for surveillance of listeriosis in ruminants are provided.

Is human herpesvirus 8 infection more common in men than in women? Systematic review and meta-analysis.

All forms of Kaposi sarcoma (KS) are more common in men than in women. It is unknown if this is due to a higher prevalence of human herpesvirus 8 (HHV-8), the underlying cause of KS, in men compared to women. We did a systematic review and meta-analysis to examine the association between HHV-8 seropositivity and gender in the general population. Studies in selected populations like for example, blood donors, hospital patients, and men who have sex with men were excluded. We searched Medline and Embase from January 1994 to February 2015. We included observational studies that recruited participants from the general population and reported HHV-8 seroprevalence for men and women or boys and girls. We used random-effects meta-analysis to pool odds ratios (OR) of the association between HHV-8 and gender. We used meta-regression to identify effect modifiers, including age, geographical region and type of HHV-8 antibody test. We included 22 studies, with 36,175 participants. Men from sub-Saharan Africa (SSA) (OR 1.21, 95% confidence interval [CI] 1.09-1.34), but not men from elsewhere (OR 0.94, 95% CI 0.83-1.06), were more likely to be HHV-8 seropositive than women (p value for interaction=0.010). There was no difference in HHV-8 seroprevalence between boys and girls from SSA (OR 0.90, 95% CI 0.72-1.13). The type of HHV-8 assay did not affect the overall results. A higher HHV-8 seroprevalence in men than women in SSA may partially explain why men have higher KS risk in this region. This article is protected by copyright. All rights reserved.