| 41. |
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| 42. |
- Nowroozalizadeh, Salma, et al.
(författare)
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Microbial Translocation Correlates with the Severity of Both HIV-1 and HIV-2 Infections
- 2010
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 201:8, s. 1150-1154
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Tidskriftsartikel (refereegranskat)abstract
- Microbial translocation has been linked to systemic immune activation during human immunodeficiency virus (HIV) type 1 infection. Here, we show that an elevated level of microbial translocation, measured as plasma lipopolysaccharide (LPS) concentration, correlates with AIDS in both individuals infected with HIV type 1 and individuals infected with HIV type 2. LPS concentration also correlates with CD4(+) T cell count and viral load independently of HIV type. Furthermore, elevated plasma LPS concentration was found to be concomitant with defective innate and mitogen responsiveness. We suggest that microbial translocation may contribute to loss of CD4(+) T cells, increase in viral load, and defective immune stimuli responsiveness during both HIV type 1 and HIV type 2 infections.
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| 43. |
- Nowroozalizadeh, Salma, et al.
(författare)
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Reply to Redd et al
- 2011
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 203:5, s. 746-746
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 44. |
- Nowroozalizadeh, Salma, et al.
(författare)
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Studies on toll-like receptor stimuli responsiveness in HIV-1 and HIV-2 infections
- 2009
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Ingår i: Cytokine. - : Elsevier BV. - 1096-0023 .- 1043-4666. ; 46:3, s. 325-331
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Tidskriftsartikel (refereegranskat)abstract
- Background: HIV-1 and HIV-2 are two related viruses with distinct clinical outcomes, where HIV-1 is more pathogenic and transmissible than HIV-2. The pathogenesis of both infections is influenced by the dysregulation and deterioration of the adaptive immune system. However, their effects on the responsiveness of innate immunity are less well known. Here, we report on toll-like receptor (TLR) stimuli responsiveness in HIV-1 or HIV-2 infections. Methods: Whole blood from 235 individuals living in Guinea-Bissau who were uninfected, infected with HIV-1, infected with HIV-2, and/or infected with HTLV-1, was stimulated with TLR7/8 and TLR9 agonists, R-848 and unmethylated CpG DNA. After TLR7/8 and TLR9 stimuli, the expression levels of IL-12 and IFN-alpha were related to gender, age, infection status, CD4(+) T cell counts. and plasma viral load. Results: Defective TLR9 responsiveness was observed in the advanced disease stage, along with CD4(+) T cell loss in both HIV-1 and HIV-2 infections. Moreover, TLR7/8 responsiveness was reduced in HIV-1 infected individuals compared with uninfected controls. Conclusions: Innate immunity responsiveness can be monitored by whole blood stimulation. Both advanced HIVA and HIV-2 infections may cause innate immunity dysregulation. (C) 2009 Elsevier Ltd. All rights reserved.
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| 45. |
- Olsen, Birgitta, 1952-, et al.
(författare)
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Phenotypic and genetic characterisation of bacterial sexually transmitted infections in Bissau, Guinea-Bissau, West Africa : a prospective cohort study
- 2012
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Ingår i: BMJ Open. - London, United Kingdom : BMJ Publishing Group Ltd. - 2044-6055. ; 20:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Knowledge regarding characteristics and transmission of Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium and antibiotic resistance in N gonorrhoeae in Guinea-Bissau, West Africa, is entirely lacking.Objectives: To characterise N gonorrhoeae, C trachomatis and M genitalium samples from Guinea-Bissau and to define bacterial populations, possible transmission chains and for N gonorrhoeae spread of antibiotic-resistant isolates.Design: Prospective cohort study.Setting: Two sexual health and family planning clinics, Bissau, Guinea-Bissau.Participants: Positive samples from 711 women and 27 men.Material and methods: Positive samples for N gonorrhoeae (n=31), C trachomatis (n=60) and M genitalium (n=30) were examined. The gonococcal isolates were characterised with antibiograms, serovar determination and N gonorrhoeae multiantigen sequence typing (NG-MAST). The C trachomatis ompA gene and the M genitalium mgpB gene were sequenced, and phylogenetic analyses were performed.Results: For N gonorrhoeae, the levels of resistance (intermediate susceptibility) to ciprofloxacin, erythromycin, rifampicin, ampicillin, tetracycline, penicillin G and cefuroxime were 10% (0%), 6% (10%), 13% (10%), 68% (0%), 74% (0%), 68% (16%) and 0% (84%), respectively. All isolates were susceptible to cefixime, ceftriaxone, spectinomycin and azithromycin, and the minimum inhibitory concentrations of kanamycin (range: 8-32 mg/l) and gentamicin (range: 0.75-6 mg/l) were low (no resistance breakpoints exist for these antimicrobials). 19 NG-MAST sequence types (STs) (84% novel STs) were identified. Phylogenetic analysis of the C trachomatis ompA gene revealed genovar G as most prevalent (37%), followed by genovar D (19%). 23 mgpB STs were found among the M genitalium isolates, and 67% of isolates had unique STs.Conclusions: The diversity among the sexually transmitted infection (STI) pathogens may be associated with suboptimal diagnostics, contact tracing, case reporting and epidemiological surveillance. In Guinea-Bissau, additional STI studies are vital to estimate the STI burden and form the basis for a national sexual health strategy for prevention, diagnosis and surveillance of STIs.
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| 46. |
- Palm, Angelica A., et al.
(författare)
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Interferon Alpha-Inducible Protein 27 Expression Is Linked to Disease Severity in Chronic Infection of Both HIV-1 and HIV-2
- 2022
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Ingår i: Frontiers in Virology. - : Frontiers Media SA. - 2673-818X. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Disease progression is slower in HIV-2, as compared with HIV-1 infection, in accordance with low or undetectable plasma viremia at viral setpoint. However, it is unclear why most HIV-2 infected individuals are still at risk of developing AIDS. To explore if specific host responses are linked to HIV disease severity, we have compared blood gene expression profiles between HIV seronegative and HIV-1, HIV-2 or dually HIV-1/HIV-2 infected individuals. In this study the gene encoding Interferon alpha-inducible protein 27 (IFI27) was found to be the most differentially expressed. Detailed expression analysis revealed significantly higher IFI27 expression in HIV infected individuals compared with seronegative individuals, irrespectively of HIV type. Moreover, IFI27 expression was higher in HIV-1 than in HIV-2 infected individuals. Multiple linear regression analysis, adjusting for age and sex, showed also that plasma viral load was the strongest predictor of IFI27 expression, followed by CD4% and HIV type. In line with this, IFI27 expression was found to be higher in HIV-2 viremic, compared with HIV-2 aviremic individuals. Still, HIV-2 aviremic individuals displayed elevated IFI27 expression compared with seronegative individuals. Furthermore, in HIV-2 infected individuals, IFI27 expression was also correlated with plasma markers previously linked to inflammation and disease progression in HIV infection. Taken together, our findings suggest that sustained elevation of type I interferon signaling, here reflected by elevated IFI27 expression in the chronic infection phase, is a key pathogenic feature of both HIV-1 and HIV-2
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| 47. |
- Palm, Angelica A., et al.
(författare)
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Intra-Patient Evolution of HIV-2 Molecular Properties
- 2022
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 14:11
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Tidskriftsartikel (refereegranskat)abstract
- Limited data are available on the pathogenesis of HIV-2, and the evolution of Env molecular properties during disease progression is not fully elucidated. We investigated the intra-patient evolution of molecular properties of HIV-2 Env regions (V1–C3) during the asymptomatic, treatment-naïve phase of the infection in 16 study participants, stratified into faster or slower progressors. Most notably, the rate of change in the number of potential N-linked glycosylation sites (PNGS) within the Env (V1–C3) regions differed between progressor groups. With declining CD4+ T-cell levels, slower progressors showed, on average, a decrease in the number of PNGSs, while faster progressors showed no significant change. Furthermore, diversity increased significantly with time in faster progressors, whereas no such change was observed in slower progressors. No differences were identified between the progressor groups in the evolution of length or charge of the analyzed Env regions. Predicted virus CXCR4 use was rare and did not emerge as a dominating viral population during the studied disease course (median 7.9 years, interquartile range [IQR]: 5.2–14.0) in either progressor groups. Further work building on our observations may explain molecular hallmarks of HIV-2 disease progression and differences in pathogenesis between HIV-1 and HIV-2.
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| 48. |
- Palm, Angelica A., et al.
(författare)
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Low Postseroconversion CD4+ T-cell Level Is Associated with Faster Disease Progression and Higher Viral Evolutionary Rate in HIV-2 Infection
- 2019
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Ingår i: mBio. - 2161-2129. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- A positive correlation between virus evolutionary rate and disease progression has been shown for human immunodeficiency virus type 1 (HIV-1) infection. Much less is known about HIV-2, the second causative agent of AIDS. We analyzed 528 HIV-2 env V1-C3 sequences generated from longitudinal plasma samples that were collected from 16 study participants during a median observation time of 7.9 years (interquartile range [IQR], 5.2 to 14.0 years). Study participants were classified as faster or slower disease progressors based on longitudinal CD4+ T-cell data. The HIV-2 evolutionary rate was significantly associated with CD4+ T-cell levels and was almost twice as high among the faster progressors as among the slower progressors. Higher evolutionary rates were accounted for by both synonymous and nonsynonymous nucleotide substitutions. Moreover, slow disease progression was associated with stronger positive selection on HIV-2/SIVsm (simian immunodeficiency virus infecting sooty mangabey) surface-exposed conserved residues. This study demonstrated a number of previously unknown characteristics linking HIV-2 disease progression with virus evolution. Some of these findings distinguish HIV-2 from HIV-1 and may contribute to the understanding of differences in pathogenesis.IMPORTANCE The relationship between HIV evolution and disease progression is fundamental to our understanding of HIV immune control and vaccine design. There are no clear definitions for faster and slower HIV-2 disease progression and for the relationship of the rate of progression with HIV-2 evolution. To address the hypothesis that viral evolution is correlated with disease progression in HIV-2 infection, we determined faster and slower disease progression based on follow-up data from a prospective cohort of police officers in Guinea-Bissau. The analysis showed that although the CD4+ T-cell level and the decline in the level were independently associated with progression to AIDS, only the CD4+ T-cell level or a combined CD4+ T-cell level/decline stratification was associated with the rate of HIV-2 evolution. The HIV-2 evolutionary rate was almost twice as high among the faster progressors as among the slower progressors. Importantly, this report defines previously unknown characteristics linking HIV-2 disease progression with virus evolution.
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| 49. |
- Palm, Angelica, et al.
(författare)
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Co-circulation of several similar but unique HIV-1 recombinant forms in Guinea-Bissau revealed by near full-length genomic sequencing.
- 2015
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Ingår i: AIDS Research and Human Retroviruses. - 1931-8405. ; 31:9, s. 938-945
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Tidskriftsartikel (refereegranskat)abstract
- The dynamic HIV-1 epidemic has resulted in the emergence of several different subtypes and recombinant forms that may differ in biological properties. A recombinant form of CRF02_AG and sub-subtype A3 (A3/02) was recently described based on env sequencing and associated with faster disease progression rates compared with its parental strains. Here, we performed near full-length sequencing of the A3/02 variant to characterize the recombination patterns of a potential novel and more pathogenic circulating recombinant form of HIV-1 in Guinea-Bissau.
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| 50. |
- Palm, Angelica, et al.
(författare)
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Faster progression to AIDS and AIDS-related death among seroincident individuals infected with recombinant HIV-1 A3/CRF02_AG compared to sub subtype A3.
- 2014
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 209:5, s. 721-728
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Tidskriftsartikel (refereegranskat)abstract
- HIV-1 is divided into different subtypes and circulating recombinant forms (CRFs) but the impact of HIV-1 subtype/CRF on disease progression is not fully understood. We determined the HIV-1 subtype/CRF of 152 seroincident individuals from Guinea-Bissau, based on the C2-V3 region of env. Rate of disease progression was measured as time from estimated seroconversion to AIDS and AIDS-related death. Hazard ratios (HRs) were calculated using a Cox proportional hazard model, adjusting for gender and age at seroconversion. The major subtypes/CRFs identified were CRF02_AG (53%), A3 (29%) and A3/02 (a recombinant of A3 and CRF02_AG) (13%). Infection with A3/02 was associated with a close to 3-fold increased risk of AIDS and AIDS-related death compared to A3 (HR=2.6 [P=0.011] and 2.9 [P=0.032], respectively). The median estimated time from seroconversion to AIDS and AIDS-related death was 5.0 and 8.0 years for A3/02, 6.2 and 9.0 years for CRF02_AG and 7.2 and 11.3 years for A3. Our results show that there are significant differences in disease progression between HIV-1 A-like subtypes/CRFs. Individuals infected with the A3/02 recombinant have among the fastest progression rates to AIDS reported to date. Determining the HIV-1 subtype of infected individuals could be of importance in the management of HIV-1 infections.
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