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1.
BMC Infect Dis ; 19(1): 588, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277590

RESUMO

BACKGROUND: HIV controllers (HICs) are a rare group of HIV-1-infected individuals able to naturally control viral replication. Several studies have identified the occurrence of HIV dual infections in seropositive individuals leading to disease progression. In HICs, however, dual infections with divergent outcomes in pathogenesis have been described. CASE PRESENTATION: Here, we present a case report of a HIC diagnosed in late 1999 who displayed stable CD4+ T cell levels and low plasmatic viral load across 12 years of follow-up. In early 2013, the patient started to present an increase in viral load, reaching a peak of 10,000 copies/ml in early 2014, followed by an oscillation of viremia at moderate levels in the following years. The genetic diversity of env proviral quasispecies from peripheral blood mononuclear cells (PBMCs) was studied by single genome amplification (SGA) at six timepoints across 2009-2017. Phylogenetic analyses of env sequences from 2009 and 2010 samples showed the presence of a single subtype B variant (called B1). Analyses of sequences from 2011 and after revealed an additional subtype B variant (called B2) and a subsequent dominance shift in the proviral quasispecies frequencies, with the B2 variant becoming the most frequent from 2014 onwards. Latent syphilis related to unprotected sexual intercourse was diagnosed a year before the first detection of B2, evidencing risk behavior and supporting the superinfection hypothesis. Immunologic analyses revealed an increase in CD8+ and CD4+ T cell immune activation following viremia increase and minor T cell subset alterations during follow-up. HIV-specific T cell responses remained low throughout the follow-up period. CONCLUSIONS: Altogether, these results show that loss of viremia control in the HIC was associated with superinfection. These data alert to the negative consequences of reinfection on HIV pathogenesis, even in patients with a long history of viremia control and an absence of disease progression, reinforcing the need for continued use of adequate prevention strategies.


Assuntos
Infecções por HIV/virologia , HIV-1/fisiologia , Superinfecção/virologia , Replicação Viral/fisiologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , Feminino , Seguimentos , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , HIV-1/patogenicidade , Antígenos HLA-B/genética , Humanos , Leucócitos Mononucleares/virologia , Masculino , Filogenia , RNA Viral/sangue , Sífilis/diagnóstico , Carga Viral , Viremia/tratamento farmacológico , Viremia/virologia
2.
World J Gastroenterol ; 25(13): 1566-1579, 2019 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-30983817

RESUMO

BACKGROUND: Hepatitis delta virus (HDV) seems to strongly suppress hepatitis B virus (HBV) replication, although little is known about the mechanism of this interaction. Both these viruses show a dynamic distribution of mutants, resulting in viral quasispecies. Next-generation sequencing is a viable approach for analyzing the composition of these mutant spectra. As the regulatory hepatitis B X protein (HBx) is essential for HBV replication, determination of HBV X gene (HBX) quasispecies complexity in HBV/HDV infection compared to HBV mono-infection may provide information on the interactions between these two viruses. AIM: To compare HBV quasispecies complexity in the HBX 5' region between chronic hepatitis delta (CHD) and chronic HBV mono-infected patients. METHODS: Twenty-four untreated patients were included: 7/24 (29.2%) with HBeAg-negative chronic HBV infection (CI, previously termed inactive carriers), 8/24 (33.3%) with HBeAg-negative chronic hepatitis B (CHB) and 9/24 (37.5%) with CHD. A serum sample from each patient was first tested for HBV DNA levels. The HBX 5' region [nucleotides (nt) 1255-1611] was then PCR-amplified for subsequent next-generation sequencing (MiSeq, Illumina, United States). HBV quasispecies complexity in the region analyzed was evaluated using incidence-based indices (number of haplotypes and number of mutations), abundance-based indices (Hill numbers of order 1 and 2), and functional indices (mutation frequency and nucleotide diversity). We also evaluated the pattern of nucleotide changes to investigate which of them could be the cause of the quasispecies complexity. RESULTS: CHB patients showed higher median HBV-DNA levels [5.4 logIU/mL, interquartile range (IQR) 3.5-7.9] than CHD (3.4 logIU/mL, IQR 3-7.6) (P = n.s.) or CI (3.2 logIU/mL, IQR 2.3-3.5) (P < 0.01) patients. The incidence and abundance indices indicated that HBV quasispecies complexity was significantly greater in CI than CHB. A similar trend was observed in CHD patients, although only Hill numbers of order 2 showed statistically significant differences (CHB 2.81, IQR 1.11-4.57 vs CHD 8.87, 6.56-11.18, P = 0.038). There were no significant differences in the functional indices, but CI and CHD patients also showed a trend towards greater complexity than CHB. No differences were found for any HBV quasispecies complexity indices between CHD and CI patients. G-to-A and C-to-T nucleotide changes, characteristic of APOBEC3G, were higher in CHD and CI than in CHB in genotype A haplotypes, but not in genotype D. The proportion of nt G-to-A vs A-to-G changes and C-to-T vs T-to-C changes in genotype A and D haplotypes in CHD patients showed no significant differences. In CHB and CI the results of these comparisons were dependent on HBV genotype. CONCLUSION: The lower-replication CHD and CI groups show a trend to higher quasispecies complexity than the higher-replication CHB group. The mechanisms associated with this greater complexity require elucidation.


Assuntos
Hepatite B Crônica/virologia , Hepatite D Crônica/virologia , Quase-Espécies/genética , Superinfecção/virologia , Transativadores/genética , Adulto , Feminino , Haplótipos/genética , Vírus da Hepatite B/isolamento & purificação , Vírus da Hepatite B/fisiologia , Vírus Delta da Hepatite/isolamento & purificação , Vírus Delta da Hepatite/fisiologia , Humanos , Masculino , Replicação Viral/genética
3.
Eur J Pharmacol ; 833: 379-391, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29935174

RESUMO

An estimated 240 million people worldwide are chronically infected with the hepatitis B virus (HBV). Despite readily available vaccination, HBV infections remain highly prevalent. As established HBV infections constitute a strong risk factor for developing hepatocellular carcinoma their treatment is a major task for the health system. Unfortunately, HBV is not curable with today's medicine. Approximately 15 million HBV patients have developed a hepatitis delta (HDV) infection on top of their HBV infection. The patients superinfected with this satellite virus suffer from a more severe disease development. The knowledge of the viruses, their classifications, clinical implications, treatment options and efforts to increase the drug variety are compiled in this review. The current standard therapies include nucleosidic reverse transcriptase inhibitors and interferon. As the known treatments fail to cure HBV and HDV, targeted treatment is highly warranted. The focus of this review is set on the drugs currently under clinical investigation. Furthermore, strategies for the development of targeted treatment, and compounds with novel mode of action are described.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite D/tratamento farmacológico , Superinfecção/tratamento farmacológico , Antivirais/farmacologia , Antivirais/normas , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/prevenção & controle , Carcinoma Hepatocelular/virologia , Ensaios Clínicos como Assunto , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/transmissão , Hepatite B Crônica/virologia , Hepatite D/epidemiologia , Hepatite D/transmissão , Hepatite D/virologia , Vírus Delta da Hepatite/efeitos dos fármacos , Hepatócitos/virologia , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/virologia , Guias de Prática Clínica como Assunto , Prevalência , Superinfecção/epidemiologia , Superinfecção/virologia , Resultado do Tratamento , Replicação Viral/efeitos dos fármacos
4.
BMJ Case Rep ; 20182018 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-29891510

RESUMO

Reactivation of chronic hepatitis B (CHB) can be associated with significant morbidity and mortality. There are many different causes of hepatitis B reactivation. This case describes an Asian woman with stable CHB presenting with significant hepatitis flare with markedly elevated serum aminotransferases and hepatitis B virus DNA level. The clinical symptoms were subtle with fatigue and vague right upper quadrant tenderness. We ruled out drug-associated hepatotoxicity and screened for common causes of acute hepatitis. Interestingly, she was noted to have reactive anti-hepatitis E virus (HEV) IgM at initial presentation followed by anti-HEV IgG positivity a month later. The serological pattern confirmed the diagnosis of acute hepatitis E. The combination of antiviral therapy for hepatitis B and resolution of acute hepatitis E resulted in normalisation of serum aminotransferases. This case illustrates the importance of taking a careful history and having a high index of suspicion for various aetiologies when evaluating patients with reactivation of CHB.


Assuntos
Hepatite B Crônica/diagnóstico , Hepatite E/diagnóstico , Superinfecção/diagnóstico , Ativação Viral , Adulto , DNA Viral/sangue , Feminino , Vírus da Hepatite B/genética , Humanos , Superinfecção/virologia
5.
Viruses ; 10(5)2018 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-29783672

RESUMO

Superinfection of Marek's disease virus (MDV) and avian leukosis virus subgroup J (ALV-J) causes lethal neoplasia and death in chickens. However, whether there is synergism between the two viruses in viral replication and pathogenicity has remained elusive. In this study, we found that the superinfection of MDV and ALV-J increased the viral replication of the two viruses in RNA and protein level, and synergistically promoted the expression of IL-10, IL-6, and TGF-ß in chicken embryo fibroblasts (CEF). Moreover, MDV and ALV-J protein expression in dual-infected cells detected by confocal laser scanning microscope appeared earlier in the cytoplasm and the nucleus, and caused more severe cytopathy than single infection, suggesting that synergistically increased MDV and ALV-J viral-protein biosynthesis is responsible for the severe cytopathy. In vivo, compared to the single virus infected chickens, the mortality and tumor formation rates increased significantly in MDV and ALV-J dual-infected chickens. Viral loads of MDV and ALV-J in tissues of dual-infected chickens were significantly higher than those of single-infected chickens. Histopathology observation showed that more severe inflammation and tumor cells metastases were present in dual-infected chickens. In the present study, we concluded that synergistic viral replication of MDV and ALV-J is responsible for the enhanced pathogenicity in superinfection of chickens.


Assuntos
Vírus da Leucose Aviária/patogenicidade , Mardivirus/patogenicidade , Superinfecção/virologia , Animais , Leucose Aviária/virologia , Vírus da Leucose Aviária/fisiologia , Galinhas/virologia , Mediadores da Inflamação/metabolismo , Mardivirus/fisiologia , Doença de Marek/virologia , Carga Viral , Virulência , Replicação Viral
6.
PLoS One ; 13(4): e0195679, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29624605

RESUMO

INTRODUCTION: HIV-1 dual infection is a condition that results from infection with at least two HIV-1 variants from different sources. The scarceness of information on this condition is partly due to the fact that its detection is technically challenging. Using next-generation sequencing we defined the extent of HIV-1 dual infection in a cohort of men who have sex with men (MSM). MATERIAL & METHODS: Eighty-six MSM, diagnosed with HIV-1 subtype B infection between 2008 and 2013 were selected for next-generation sequencing of the HIV-1 envelope V3. Sequencing was performed on 2 plasma samples collected with an interval of > 6 months before the initiation of antiretroviral therapy. Maximum likelihood phylogenetic trees were inspected for dual infection, defined as the presence of two or more monophyletic clusters with ≥ 90% bootstrap support and a mean between-cluster genetic distance of ≥ 10%. To confirm dual infection, deep V3 sequencing of intermediate samples was performed as well as clonal sequencing of the HIV-1 protease-reverse transcriptase gene. RESULTS: Five of the 74 patients (6.8%) for whom deep sequencing was successful, showed clear evidence of dual infection. In 4 of them, the second strain was absent in the first sample but occurred in subsequent samples. This was highly suggestive for superinfection. In 3 patients both virus variants were of subtype B, in 2 patients at least one of the variants was a subtype B/non-B recombinant virus. CONCLUSIONS: Dual infection was confirmed in 6.8% of MSM diagnosed with HIV-1 in Belgium. This prevalence is probably an underestimation, because stringent criteria were used to classify viral variants as originating from a new infection event.


Assuntos
Infecções por HIV/epidemiologia , HIV-1 , Adulto , Bélgica/epidemiologia , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Sequenciamento de Nucleotídeos em Larga Escala , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/genética , Filogenia , Prevalência , Pirróis , Estudos Retrospectivos , Superinfecção/epidemiologia , Superinfecção/virologia
7.
Microbiol Immunol ; 62(3): 141-149, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29377225

RESUMO

Group A Streptococcus (GAS) are pathogenic bacteria of the genus Streptococcus and cause severe invasive infections that comprise a wide range of diverse diseases, including acute respiratory distress syndrome, renal failure, toxic shock-like syndrome, sepsis, cellulitis and necrotizing fasciitis. The essential virulence, infected host and external environmental factors required for invasive GAS infections have not yet been determined. Superinfection with influenza virus and GAS induced invasive GAS infections was demonstrated by our team in a mouse model, after which clinical cases of invasive GAS infections secondary to influenza virus infection were reported by other investigators in Japan, USA, Canada, UK China, and other countries. However, the pathogenic mechanisms underlying influenza virus-GAS superinfection are not yet fully understood. The present review describes the current knowledge about invasive GAS infections by superinfection. Topics addressed include the bacteriological, virological and immunological mechanisms impacting invasion upon superinfection on top of underlying influenza virus infection by GAS and other bacteria (i.e., Streptococcus pneumoniae and Staphylococcus aureus). Future prospects are also discussed.


Assuntos
Vírus da Influenza A/patogenicidade , Infecções por Orthomyxoviridae/complicações , Orthomyxoviridae/patogenicidade , Infecções Estreptocócicas/complicações , Superinfecção/complicações , Animais , Aderência Bacteriana , Coinfecção/complicações , Coinfecção/imunologia , Coinfecção/microbiologia , Coinfecção/virologia , Células Epiteliais , Humanos , Influenza Humana/virologia , Camundongos , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Staphylococcus aureus/patogenicidade , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/virologia , Streptococcus pyogenes/patogenicidade , Superinfecção/imunologia , Superinfecção/microbiologia , Superinfecção/virologia , Virulência , Fatores de Virulência
8.
Retrovirology ; 15(1): 7, 2018 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-29338738

RESUMO

BACKGROUND: The factors determining differential HIV disease outcome among individuals expressing protective HLA alleles such as HLA-B*27:05 and HLA-B*57:01 remain unknown. We here analyse two HIV-infected subjects expressing both HLA-B*27:05 and HLA-B*57:01. One subject maintained low-to-undetectable viral loads for more than a decade of follow up. The other progressed to AIDS in < 3 years. RESULTS: The rapid progressor was the recipient within a known transmission pair, enabling virus sequences to be tracked from transmission. Progression was associated with a 12% Gag sequence change and 26% Nef sequence change at the amino acid level within 2 years. Although next generation sequencing from early timepoints indicated that multiple CD8+ cytotoxic T lymphocyte (CTL) escape mutants were being selected prior to superinfection, < 4% of the amino acid changes arising from superinfection could be ascribed to CTL escape. Analysis of an HLA-B*27:05/B*57:01 non-progressor, in contrast, demonstrated minimal virus sequence diversification (1.1% Gag amino acid sequence change over 10 years), and dominant HIV-specific CTL responses previously shown to be effective in control of viraemia were maintained. Clonal sequencing demonstrated that escape variants were generated within the non-progressor, but in many cases were not selected. In the rapid progressor, progression occurred despite substantial reductions in viral replicative capacity (VRC), and non-progression in the elite controller despite relatively high VRC. CONCLUSIONS: These data are consistent with previous studies demonstrating rapid progression in association with superinfection and that rapid disease progression can occur despite the relatively the low VRC that is typically observed in the setting of multiple CTL escape mutants.


Assuntos
Progressão da Doença , Infecções por HIV/virologia , HIV-1/fisiologia , Superinfecção/virologia , Substituição de Aminoácidos , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Análise por Conglomerados , Epitopos de Linfócito T/genética , Variação Genética , Proteína do Núcleo p24 do HIV/genética , Infecções por HIV/genética , Infecções por HIV/imunologia , HIV-1/classificação , HIV-1/genética , HIV-1/imunologia , Antígenos HLA-B/imunologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , RNA Viral/sangue , RNA Viral/genética , Análise de Sequência de RNA , Superinfecção/genética , Superinfecção/imunologia , Linfócitos T Citotóxicos/imunologia , Carga Viral , Replicação Viral , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética
9.
Transpl Infect Dis ; 20(1)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29111605

RESUMO

Influenza infection and Pneumocystis jirovecii pneumonia (PJP) in hematopoietic stem cell transplant (HSCT) patients are well characterized; however, no dual infections have been reported in this patient population and little evidence of mechanisms of interaction between the two infections exists. We present a 53-year-old male allogeneic HSCT patient on immunosuppressive therapy for the treatment of graft versus host disease initially diagnosed with influenza A H3 and later PJP. Despite the development of acute respiratory distress syndrome, the patient was successfully treated with appropriate antimicrobial therapy and aggressive supportive care. This case demonstrates the necessity of maintaining a high index of suspicion for fungal (including PJP) coinfection or superinfection in the setting of worsening influenza infection.


Assuntos
Coinfecção/microbiologia , Coinfecção/virologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Influenza Humana/virologia , Pneumonia por Pneumocystis/microbiologia , Superinfecção , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Hospedeiro Imunocomprometido , Imunossupressores , Influenza Humana/etiologia , Masculino , Pessoa de Meia-Idade , Pneumocystis carinii/efeitos dos fármacos , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/etiologia , Fatores de Risco , Superinfecção/microbiologia , Superinfecção/virologia , Transplante Homólogo/efeitos adversos
10.
Front Med ; 11(4): 480-489, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29170914

RESUMO

Superinfection is frequently detected among individuals infected by human immunodeficiency virus type I (HIV-1). Superinfection occurs at similar frequencies at acute and chronic infection stages but less frequently than primary infection. This observation indicates that the immune responses elicited by natural HIV-1 infection may play a role in curb of superinfection; however, these responses are not sufficiently strong to completely prevent superinfection. Thus, a successful HIV-1 vaccine likely needs to induce more potent and broader immune responses than those elicited by primary infection. On the other hand, potent and broad neutralization responses are more often detected after superinfection than during monoinfection. This suggests that broadly neutralizing antibodies are more likely induced by sequential immunization of multiple different immunogens than with only one form of envelope glycoprotein immunogens. Understanding why the protection from superinfection by immunity induced by primary infection is insufficient and if superinfection can lead to cross-reactive immune responses will be highly informative for HIV-1 vaccine design.


Assuntos
Infecções por HIV/imunologia , HIV-1/fisiologia , Superinfecção , Anticorpos Neutralizantes , Humanos , Imunidade Humoral , Superinfecção/imunologia , Superinfecção/virologia
11.
Virology ; 511: 222-228, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28888112

RESUMO

The mechanism of cross-protection, the deliberate infection of plants with a "mild" virus isolate to protect against "severe" isolates, has long been a topic of debate. In our model system, Citrus tristeza virus (CTV), this appears to be genotype-specific superinfection-exclusion, suggesting a simple recipe for cross-protection. However, this concept failed in field trials, which led us to examine the process of superinfection-exclusion more closely. We found that exclusion relies on the relative fitness of the primary versus the challenge isolates, and the host infected, and that significant differences in superinfection success could occur between isolates that differ by as few as 3 nucleotides. Furthermore, we found that exclusion was not uniform throughout the plant, but was tissue-specific. These data suggest that cross-protection is not a simple like-for-like process but a complex interaction between the primary and challenge isolates and the host.


Assuntos
Citrus/virologia , Closterovirus/fisiologia , Doenças das Plantas/virologia , Superinfecção/virologia , Interferência Viral , Tropismo Viral , Interações Hospedeiro-Patógeno
12.
J Clin Virol ; 96: 44-48, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28950185

RESUMO

BACKGROUND: Norovirus causes chronic infections in immunocompromised patients with considerable associated morbidity. It is not known whether chronic infections involve super- or re-infections or relapses. OBJECTIVES: To retrospectively investigate whether longitudinal sampling in chronically infected patients demonstrates persistent infection with the same virus, or super- or re-infection. STUDY DESIGN: Norovirus full genomes were generated from 86 longitudinal samples from 25 paediatric patients. Consensus sequences were used for phylogenetic analysis and genotyping. RESULTS: Super-infections occurred in 17% of chronically infected patients who were continuously PCR positive; including two with mixed norovirus infections. The median duration of infection was 107days longer in those with super-infections; however this was not statistically significant. A third of patients with interrupted norovirus shedding continued to be infected with the same virus despite up to 2 months of PCR negative stools, classified as a relapse. The majority (67%) of patients with interrupted shedding were re-infected with a different genotype. CONCLUSIONS: Chronically infected patients who are continuously PCR positive are most likely to remain infected with the same virus; however super-infections do occur leading to mixed infection. Patients with interrupted shedding are likely to represent re-infection with a different genotype, however relapsing infections also occur. Our findings have implications for infection control as immunosuppressed patients remain susceptible to new norovirus infections despite current or recent infection and may continue to be infectious after norovirus is undetectable in stool. The relevance to children without co-morbidities remains to be determined.


Assuntos
Infecções por Caliciviridae/epidemiologia , Infecções por Caliciviridae/virologia , Norovirus/classificação , Norovirus/isolamento & purificação , Recidiva , Superinfecção/epidemiologia , Superinfecção/virologia , Adolescente , Criança , Pré-Escolar , Doença Crônica , Feminino , Técnicas de Genotipagem , Humanos , Lactente , Estudos Longitudinais , Masculino , Norovirus/genética , Estudos Retrospectivos , Análise de Sequência de DNA
13.
J Virol ; 91(17)2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28615205

RESUMO

Understanding whether the neutralizing antibody (NAb) response impacts HIV-1 superinfection and how superinfection subsequently modulates the NAb response can help clarify correlates of protection from HIV exposures and better delineate pathways of NAb development. We examined associations between the development of NAb and the occurrence of superinfection in a well-characterized, antiretroviral therapy (ART)-naive, primary infection cohort of men who have sex with men. Deep sequencing was applied to blood plasma samples from the cohort to detect cases of superinfection. We compared the NAb activity against autologous and heterologous viruses between 10 participants with intrasubtype B superinfection and 19 monoinfected controls, matched to duration of infection and risk behavior. Three to 6 months after primary infection, individuals who would later become superinfected had significantly weaker NAb activity against tier 1 subtype B viruses (P = 0.003 for SF-162 and P = 0.017 for NL4-3) and marginally against autologous virus (P = 0.054). Lower presuperinfection NAb responses correlated with weaker gp120 binding and lower plasma total IgG titers. Soon after superinfection, the NAb response remained lower, but between 2 and 3 years after primary infection, NAb levels strengthened and reached those of controls. Superinfecting viruses were typically not susceptible to neutralization by presuperinfection plasma. These observations suggest that recently infected individuals with a delayed NAb response against primary infecting and tier 1 subtype B viruses are more susceptible to superinfection.IMPORTANCE Our findings suggest that within the first year after HIV infection, a relatively weak neutralizing antibody response against primary and subtype-specific neutralization-sensitive viruses increases susceptibility to superinfection in the face of repeated exposures. As natural infection progresses, the immune response strengthens significantly in some superinfected individuals. These findings will inform HIV vaccine design by providing testable correlates of protection from initial HIV infection.


Assuntos
Anticorpos Anti-HIV/imunologia , Infecções por HIV/imunologia , HIV-1/classificação , Superinfecção/imunologia , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , California , Estudos de Casos e Controles , Anticorpos Anti-HIV/sangue , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/virologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Testes de Neutralização , Superinfecção/virologia , Adulto Jovem
14.
J Acquir Immune Defic Syndr ; 75(4): 480-487, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28490044

RESUMO

BACKGROUND: Considerable numbers of HIV-1-infected men who have sex with men (MSM) show a relatively rapid disease progression in China; however, the cause remains elusive. HIV-1 dual infection was reported to occur commonly among the MSM population, and its contribution to clinical prognosis remains controversial. We investigated the occurrence and impact on disease progression of dual infection in a prospective MSM cohort in China. METHODS: Sixty-four HIV-1 early-infected participants were longitudinally followed up for 2 years. Deep sequencing was used as dual-infection screening. CD4 T-cell counts and HIV-1 viral load were compared between coinfection and single-infection participants and pre- versus post-superinfection. RESULTS: Eight coinfected participants and 10 superinfected participants were identified, including 9 participants with intersubtype and 9 with intrasubtype dual infections. The prevalence of coinfection was 13.1%, with a superinfection incidence of 15.6%. Coinfection participants showed lower CD4 T-cell counts at 120 days after infection (P = 0.042) and a higher viral set point tendency (P = 0.053) as compared with single-infection participants. Kaplan-Meier analysis showed that the time for the viral load to increase to above 4 log10 copies per milliliter was shorter in coinfection participants than in single-infection participants (P < 0.001). After superinfection, the median CD4 T-cell count decreased from 635 to 481 cells/µL (P = 0.027). CONCLUSIONS: The occurrence of dual infection among Chinese MSM is relatively high, and HIV-1 dual infection might contribute to rapid disease progression seen in the MSM population.


Assuntos
Coinfecção , Progressão da Doença , Infecções por HIV , Homossexualidade Masculina , Superinfecção , Adulto , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , China , Coinfecção/diagnóstico , Coinfecção/imunologia , Coinfecção/virologia , Infecções por HIV/diagnóstico , Infecções por HIV/genética , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Estudos Longitudinais , Masculino , Prognóstico , Estudos Prospectivos , RNA Viral/análise , RNA Viral/genética , Superinfecção/imunologia , Superinfecção/virologia , Carga Viral/genética , Carga Viral/imunologia , Adulto Jovem
15.
EBioMedicine ; 18: 216-224, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28427948

RESUMO

HIV-1 superinfection, in which an infected individual acquires a second HIV-1 infection from a different partner, is one of the only settings in which HIV acquisition occurs in the context of a pre-existing immune response to natural HIV infection. There is evidence that initial infection provides some protection from superinfection, particularly after 6months of initial infection, when development of broad immunity occurs. Comparison of the immune response of superinfected individuals at the time of superinfection acquisition to that of individuals who remain singly infected despite continued exposure can shed light on immune correlates of HIV acquisition to inform prophylactic vaccine design. We evaluated a panel of humoral immune responses in the largest published group of superinfected individuals (n=21), compared to a set of 3:1 matched singly infected controls from the same cohort. The immune functions studied included plasma neutralization, plasma and cervical antibody-dependent cellular cytotoxicity, and plasma IgG and IgA binding to a panel of 18 envelope antigens, including correlates of HIV acquisition in the RV144 vaccine trial, IgG binding to V1V2 and IgA binding to gp140. Association between each immune function and HIV superinfection was evaluated using conditional logistic regression. No significant associations were detected between any of the immune functions and superinfection acquisition. This study constitutes the most comprehensive and detailed characterization of multiple immune correlates of superinfection to date. The results suggest that immune responses not commonly measured in current HIV studies may be important in protection from HIV infection, and these or a more robust humoral response than that seen in naturally infected women may be needed for a protective vaccine.


Assuntos
Infecções por HIV/patologia , Imunidade Humoral , Superinfecção/patologia , Adulto , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Citotoxicidade Celular Dependente de Anticorpos , Reações Antígeno-Anticorpo , Feminino , Anticorpos Anti-HIV/sangue , Anticorpos Anti-HIV/imunologia , Antígenos HIV/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/genética , HIV-1/metabolismo , HIV-1/patogenicidade , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Quênia , Mutação , Risco , Superinfecção/imunologia , Superinfecção/virologia
16.
PLoS One ; 12(3): e0173705, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28288209

RESUMO

HIV superinfection describes the sequential infection of an individual with two or more unrelated HIV strains. Intersubtype superinfection has been shown to cause a broader and more potent heterologous neutralizing antibody response when compared to singly infected controls, yet the effects of intrasubtype superinfection remain controversial. Longitudinal samples were analyzed phylogenetically for pol and env regions using Next-Generation Sequencing and envelope cloning. The impact of CRF02_AG intrasubtype superinfection was assessed for heterologous neutralization and antibody binding responses. We compared two cases of CRF02_AG intrasubtype superinfection that revealed complete replacement of the initial virus by superinfecting CRF02_AG variants with signs of recombination. NYU6564, who became superinfected at an early time point, exhibited greater changes in antibody binding profiles and generated a more potent neutralizing antibody response post-superinfection compared to NYU6501. In contrast, superinfection occurred at a later time point in NYU6501 with strains harboring significantly longer V1V2 regions with no observable changes in neutralization patterns. Here we show that CRF02_AG intrasubtype superinfection can induce a cross-subtype neutralizing antibody response, and our data suggest timing and/or superinfecting viral envelope characteristics as contributing factors. These results highlight differential outcomes in intrasubtype superinfection and provide the first insight into cases with CRF02_AG, the fourth most prevalent HIV-1 strain worldwide.


Assuntos
HIV-1/genética , HIV-1/imunologia , Superinfecção/virologia , Anticorpos Neutralizantes , Formação de Anticorpos , Epitopos/imunologia , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/patogenicidade , Humanos , Filogenia , Gravidez , Recombinação Genética , Carga Viral , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética
17.
Virus Res ; 233: 51-59, 2017 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-28279802

RESUMO

Viral infections may predispose the airways to secondary bacterial infections that can lead to unfavorable progression of principally self-limiting illnesses. Such complicated respiratory infections include pneumonia, bronchitis, sinusitis, acute otitis media, and sepsis, which cause high morbidity and lethality. Some of the pathogenic consequences of viral infections, like the expression of bacterial adhesion receptors and the disturbance of physical barrier integrity due to inflammation, may create permissive conditions for co-infections. Influenza virus A (H3N2) is a major pathogen that causes secondary bacterial infections and inflammation that lead to pneumonia. The herbal medicine Echinacea purpurea, on the other hand, has been widely used to prevent and treat viral respiratory infections, and recent clinical data suggest that it may prevent secondary infection complications as well. We investigated the role of standardized E. purpurea (Echinaforce® extract or EF) on H3N2-induced adhesion of live nontypeable Haemophilus influenzae (NTHi) and Staphylococcus aureus, along with the expression of bacterial receptors, intracellular adhesion molecule-1 (ICAM-1), fibronectin, and platelet activating factor receptor (PAFr), by BEAS-2B cells. Inflammatory processes were investigated by determining the cellular expression of IL-6 and IL-8 and the involvement of Toll-like receptor (TLR-4) and NFκB p65. We found that influenza virus A infection increased the adhesion of H. influenzae and S. aureus to bronchial epithelial cells via upregulated expression of the ICAM-1 receptor and, to some extent, of fibronectin and PAFr. Echinaforce (EF) significantly reduced the expression of ICAM-1, fibronectin, and PAFr and consequently the adhesion of both bacterial strains. EF also effectively prevented the super-expression of inflammatory cytokines by suppressing the expression of NFκB and possibly TLR-4. These results indicate that E. purpurea has the potential to reduce the risk of respiratory complications by preventing virus-induced bacterial adhesion and through the inhibition of inflammation super-stimulation (cytokine storms).


Assuntos
Anti-Infecciosos/farmacologia , Echinacea/química , Células Epiteliais/efeitos dos fármacos , Superinfecção/prevenção & controle , Receptor 4 Toll-Like/antagonistas & inibidores , Fator de Transcrição RelA/antagonistas & inibidores , Linhagem Celular , Coinfecção , Células Epiteliais/citologia , Células Epiteliais/microbiologia , Células Epiteliais/virologia , Fibronectinas/genética , Fibronectinas/imunologia , Regulação da Expressão Gênica , Haemophilus influenzae/efeitos dos fármacos , Haemophilus influenzae/crescimento & desenvolvimento , Haemophilus influenzae/patogenicidade , Interações Hospedeiro-Patógeno , Humanos , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/crescimento & desenvolvimento , Vírus da Influenza A Subtipo H3N2/patogenicidade , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Pulmão/citologia , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Pulmão/virologia , Extratos Vegetais/farmacologia , Glicoproteínas da Membrana de Plaquetas/genética , Glicoproteínas da Membrana de Plaquetas/imunologia , Receptores Acoplados a Proteínas-G/genética , Receptores Acoplados a Proteínas-G/imunologia , Transdução de Sinais , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/patogenicidade , Superinfecção/microbiologia , Superinfecção/virologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/imunologia
19.
Am J Pathol ; 187(4): 697-699, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28222276

RESUMO

This commentary highlights the article by Pociask et al that provides new insights into the lingering effects of influenza infection.


Assuntos
Influenza Humana/patologia , Pulmão/patologia , Pulmão/virologia , Animais , Modelos Animais de Doenças , Humanos , Influenza Humana/genética , Influenza Humana/virologia , Superinfecção/microbiologia , Superinfecção/virologia , Transcriptoma/genética
20.
Trop Med Int Health ; 22(4): 399-406, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28150899

RESUMO

OBJECTIVE: Dengue virus consists of four antigenically distinct serotypes (DENV 1-4) that are transmitted to humans by Aedes aegypti and Aedes albopictus mosquitoes. In many dengue-endemic regions, co-circulation of two or more DENV serotypes is fairly common increasing the likelihood for exposure of the two vectors to multiple serotypes. We used a model system of DENV-2 and DENV-4 to investigate how prior exposure of Aedes aegypti to one DENV serotype affects its susceptibility to another serotype. METHODS: Aedes aegypti mosquitoes were sequentially infected with DENV-2 and DENV-4 and the infection and dissemination rates for each virus determined. RESULTS: We found that prior infection of Ae. aegypti mosquitoes with DENV-4 rendered them significantly less susceptible to secondary infection with DENV-2. Although the results were not statistically significant, mosquitoes infected with DENV-2 were also less susceptible to secondary infection with DENV-4. The midgut dissemination and population dissemination rates for DENV-2 were significantly higher than those of DENV-4 when either virus was administered 7 days after administration of either a non-infectious blood meal or a blood meal containing a heterologous dengue serotype. CONCLUSION: These results demonstrate that superinfection interference between DENV serotypes is possible within Ae. aegypti mosquitoes, but its effect on DENV epidemiology may be dependent on the fitness of interacting serotypes.


Assuntos
Aedes/virologia , Vírus da Dengue , Dengue/transmissão , Insetos Vetores/virologia , Sorogrupo , Superinfecção/virologia , Animais , Dengue/epidemiologia , Vírus da Dengue/classificação , Humanos , Especificidade da Espécie
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