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1.
Front Endocrinol (Lausanne) ; 12: 745984, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630335

RESUMO

Although spermatogenic dysfunction is widely found in patients with human immunodeficiency virus (HIV), the underlying reasons remain unclear. Thus far, potential hypotheses involving viral reservoirs, testicular inflammation, hormone imbalance, and cachexia show inconsistent correlation with spermatogenic dysfunction. Here, northern pig-tailed macaques (NPMs) exhibited marked spermatogenic dysfunction after long-term infection with simian immunodeficiency virus (SIVmac239), with significant decreases in Johnsen scores, differentiated spermatogonial stem cells, and testicular proliferating cells. The above hypotheses were also evaluated. Results showed no differences between SIV- and SIV+ NPMs, except for an increase in follicle stimulating hormone (FSH) during SIV infection, which had no direct effect on the testes. However, long-term SIVmac239 infection undermined pancreatic islet ß cell function, partly represented by significant reductions in cellular counts and autophagy levels. Pancreatic islet ß cell dysfunction led to glucose metabolism disorder at the whole-body level, which inhibited lactate production by Sertoli cells in testicular tissue. As lactate is the main energy substrate for developing germ cells, its decrease was strongly correlated with spermatogenic dysfunction. Therefore, glucose metabolism disorder appears to be a primary cause of spermatogenic dysfunction in NPMs with long-term SIVmac239 infection.

2.
Signal Transduct Target Ther ; 6(1): 328, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471088

RESUMO

Understanding the pathological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in an animal model is crucial for the treatment of coronavirus disease 2019 (COVID-19). Here, we compared immunopathological changes in young and old rhesus macaques (RMs) before and after SARS-CoV-2 infection at the tissue level. Quantitative analysis of multiplex immunofluorescence staining images of formalin-fixed paraffin-embedded (FFPE) sections showed that SARS-CoV-2 infection specifically induced elevated levels of apoptosis, autophagy, and nuclear factor kappa-B (NF-κB) activation of angiotensin-converting enzyme 2 (ACE2)+ cells, and increased interferon α (IFN-α)- and interleukin 6 (IL-6)-secreting cells and C-X-C motif chemokine receptor 3 (CXCR3)+ cells in lung tissue of old RMs. This pathological pattern, which may be related to the age-related pro-inflammatory microenvironment in both lungs and spleens, was significantly correlated with the systemic accumulation of CXCR3+ cells in lungs, spleens, and peripheral blood. Furthermore, the ratio of CXCR3+ to T-box protein expression in T cell (T-bet)+ (CXCR3+/T-bet+ ratio) in CD8+ cells may be used as a predictor of severe COVID-19. These findings uncovered the impact of aging on the immunopathology of early SARS-CoV-2 infection and demonstrated the potential application of CXCR3+ cells in predicting severe COVID-19.


Assuntos
Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , Microambiente Celular/imunologia , Pulmão/imunologia , Receptores CXCR3/imunologia , SARS-CoV-2/imunologia , Enzima de Conversão de Angiotensina 2/imunologia , Animais , Linfócitos T CD8-Positivos/patologia , COVID-19/patologia , Modelos Animais de Doenças , Inflamação/imunologia , Inflamação/patologia , Interferon-alfa/imunologia , Interleucina-6/imunologia , Pulmão/patologia , Pulmão/virologia , Macaca mulatta , Masculino
4.
Cell Res ; 31(9): 1011-1023, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34267349

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLNs. A low dose of I-R-F induces not only high titers of long-lasting neutralizing antibodies (NAbs) but also more comprehensive T cell responses than RBD. Notably, I-R-F provides comprehensive protection in the form of a one-dose vaccine without an adjuvant. Our study shows that the pan-epitope modified human I-R-F (I-P-R-F) vaccine provides rapid and complete protection throughout the upper and lower respiratory tracts against a high-dose SARS-CoV-2 challenge in rhesus macaques. Based on these promising results, we have initiated a randomized, placebo-controlled, phase I/II trial of the human I-P-R-F vaccine (V-01) in 180 healthy adults, and the vaccine appears safe and elicits strong antiviral immune responses. Due to its potency and safety, this engineered vaccine may become a next-generation vaccine candidate in the global effort to overcome COVID-19.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Imunogenicidade da Vacina/imunologia , Ligação Proteica/imunologia , Domínios Proteicos/imunologia , SARS-CoV-2/imunologia , Adolescente , Adulto , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Antivirais/imunologia , Linhagem Celular , Chlorocebus aethiops , Método Duplo-Cego , Feminino , Células HEK293 , Humanos , Interferons/imunologia , Macaca mulatta , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Vacinação/métodos , Células Vero , Adulto Jovem
5.
Zool Res ; 42(3): 335-338, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-33998180

RESUMO

The global outbreak of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as of 8 May 2021, has surpassed 150 700 000 infections and 3 279 000 deaths worldwide. Evidence indicates that SARS-CoV-2 RNA can be detected on particulate matter (PM), and COVID-19 cases are correlated with levels of air pollutants. However, the mechanisms of PM involvement in the spread of SARS-CoV-2 remain poorly understood. Here, we found that PM exposure increased the expression level of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in several epithelial cells and increased the adsorption of the SARS-CoV-2 spike protein. Instillation of PM in a hACE2 mouse model significantly increased the expression of ACE2 and Tmprss2 and viral replication in the lungs. Furthermore, PM exacerbated the pulmonary lesions caused by SARS-CoV-2 infection in the hACE2 mice. In conclusion, our study demonstrated that PM is an epidemiological factor of COVID-19, emphasizing the necessity of wearing anti-PM masks to cope with this global pandemic.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/induzido quimicamente , COVID-19/imunologia , Material Particulado/efeitos adversos , SARS-CoV-2 , Adsorção/efeitos dos fármacos , Animais , Suscetibilidade a Doenças/induzido quimicamente , Suscetibilidade a Doenças/imunologia , Células Epiteliais/metabolismo , Camundongos , Camundongos Endogâmicos , Material Particulado/química , RNA Viral/análise , SARS-CoV-2/genética , Serina Endopeptidases/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus/efeitos dos fármacos
6.
Zool Res ; 42(3): 350-353, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-33998182

RESUMO

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), has become an unprecedented global health emergency. At present, SARS-CoV-2-infected nonhuman primates are considered the gold standard animal model for COVID-19 research. Here, we showed that northern pig-tailed macaques ( Macaca leonina, NPMs) supported SARS-CoV-2 replication. Furthermore, compared with rhesus macaques, NPMs showed rapid viral clearance in lung tissues, nose swabs, throat swabs, and rectal swabs, which may be due to higher expression of interferon (IFN)-α in lung tissue. However, the rapid viral clearance was not associated with good outcome. In the second week post infection, NPMs developed persistent or even more severe inflammation and body injury compared with rhesus macaques. These results suggest that viral clearance may have no relationship with COVID-19 progression and SARS-CoV-2-infected NPMs could be considered as a critically ill animal model in COVID-19 research.


Assuntos
COVID-19/imunologia , COVID-19/virologia , Macaca nemestrina , SARS-CoV-2/imunologia , Animais , Modelos Animais de Doenças , Interferon-alfa/análise , Interleucina-1beta/análise , Interleucina-6/análise , Pulmão/imunologia , Pulmão/virologia , Nariz/virologia , Faringe/virologia , RNA Viral/análise , Reto/virologia , SARS-CoV-2/genética
7.
Nat Commun ; 12(1): 1346, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649323

RESUMO

SARS-CoV-2 is the underlying cause for the COVID-19 pandemic. Like most enveloped RNA viruses, SARS-CoV-2 uses a homotrimeric surface antigen to gain entry into host cells. Here we describe S-Trimer, a native-like trimeric subunit vaccine candidate for COVID-19 based on Trimer-Tag technology. Immunization of S-Trimer with either AS03 (oil-in-water emulsion) or CpG 1018 (TLR9 agonist) plus alum adjuvants induced high-level of neutralizing antibodies and Th1-biased cellular immune responses in animal models. Moreover, rhesus macaques immunized with adjuvanted S-Trimer were protected from SARS-CoV-2 challenge compared to vehicle controls, based on clinical observations and reduction of viral loads in lungs. Trimer-Tag may be an important platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.


Assuntos
Vacinas contra COVID-19/uso terapêutico , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/patogenicidade , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Western Blotting , COVID-19/terapia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunidade Celular/fisiologia , Imunização Passiva , Imuno-Histoquímica , Macaca mulatta , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica , SARS-CoV-2/imunologia
8.
Zool Res ; 42(2): 252, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33738991

RESUMO

After the publication of Wang et al. (2020), we realized that there were some inappropriate statements in the content. Hereby, we correct them and apologize for any confusion this may have caused.

10.
Zool Res ; 41(5): 503-516, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32772513

RESUMO

As of June 2020, Coronavirus Disease 2019 (COVID-19) has killed an estimated 440 000 people worldwide, 74% of whom were aged ≥65 years, making age the most significant risk factor for death caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To examine the effect of age on death, we established a SARS-CoV-2 infection model in Chinese rhesus macaques ( Macaca mulatta) of varied ages. Results indicated that infected young macaques manifested impaired respiratory function, active viral replication, severe lung damage, and infiltration of CD11b + and CD8 + cells in lungs at one-week post infection (wpi), but also recovered rapidly at 2 wpi. In contrast, aged macaques demonstrated delayed immune responses with a more severe cytokine storm, increased infiltration of CD11b + cells, and persistent infiltration of CD8 + cells in the lungs at 2 wpi. In addition, peripheral blood T cells from aged macaques showed greater inflammation and chemotaxis, but weaker antiviral functions than that in cells from young macaques. Thus, the delayed but more severe cytokine storm and higher immune cell infiltration may explain the poorer prognosis of older aged patients suffering SARS-CoV-2 infection.


Assuntos
Envelhecimento/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Macaca mulatta/imunologia , Pneumonia Viral/imunologia , Linfócitos T/imunologia , Fatores Etários , Envelhecimento/metabolismo , Animais , Betacoronavirus/fisiologia , COVID-19 , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Inflamação/imunologia , Inflamação/veterinária , Inflamação/virologia , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Macaca mulatta/virologia , Doenças dos Macacos/imunologia , Doenças dos Macacos/virologia , Pandemias/veterinária , Pneumonia Viral/veterinária , Pneumonia Viral/virologia , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/veterinária , Síndrome Respiratória Aguda Grave/virologia , Linfócitos T/metabolismo , Linfócitos T/patologia , Carga Viral/imunologia , Carga Viral/veterinária , Replicação Viral/imunologia
11.
Zool Res ; 41(4): 449-454, 2020 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-32521575

RESUMO

Intestinal biopsy is a basic experimental method for studying pathological changes in the intestinal tract during human immunodeficiency virus (HIV) infection. In this study, jejunal resection and anastomosis were successfully performed in 12 Chinese rhesus macaques ( Macaca mulatta). The sampled gut tissues were then examined by hematoxylin and eosin (H&E) staining, electron microscopy, flow cytometry, immunofluorescence detection, and RNA quality analysis to ensure suitability for histological, physiological, pathological, and immunological detection, as well as mechanistic analysis at the cellular and molecular level. Importantly, the surgery did not affect the ratio or number of immune cells in peripheral blood or the concentration of lipids, proteins, and vitamins in plasma, which are important indicators of nutritional status. Our results thus indicated that jejunal resection and anastomosis are feasible, and that immune homeostasis and intestinal barrier integrity are not altered by surgery. All macaques recovered well (except for one), with no postoperative complications. Therefore, this animal surgery may be applicable for longitudinal intestinal research related to diseases such as acquired immunodeficiency syndrome (AIDS).


Assuntos
Anastomose Cirúrgica/veterinária , Jejuno/cirurgia , Macaca mulatta/cirurgia , Animais , Homeostase/imunologia , Sistema Imunitário/fisiologia , Jejuno/fisiologia , Doenças dos Macacos
12.
Zool Res ; 40(6): 522-531, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31033262

RESUMO

Microbial translocation is a cause of systemic immune activation in HIV/SIV infection. In the present study, we found a lower CD8+ T cell activation level in Macaca leonina (northern pig-tailed macaques, NPMs) than in Macaca mulatta (Chinese rhesus macaques, ChRMs) during SIVmac239 infection. Furthermore, the levels of plasma LPS-binding protein and soluble CD14 in NPMs were lower than those in ChRMs. Compared with ChRMs, SIV-infected NPMs had lower Chiu scores, representing relatively normal intestinal mucosa. In addition, no obvious damage to the ileum or colon epithelial barrier was observed in either infected or uninfected NPMs, which differed to that found in ChRMs. Furthermore, no significant microbial translocation (Escherichia coli) was detected in the colon or ileum of infected or uninfected NPMs, which again differed to that observed in ChRMs. In conclusion, NPMs retained superior intestinal integrity and limited microbial translocation during SIV infection, which may contribute to their lower immune activation compared with ChRMs.


Assuntos
Translocação Bacteriana/fisiologia , Intestinos/microbiologia , Intestinos/patologia , Macaca/fisiologia , Síndrome de Imunodeficiência Adquirida dos Símios/patologia , Vírus da Imunodeficiência Símia , Animais , Biomarcadores/sangue , Linfócitos T CD8-Positivos/fisiologia , Intestinos/fisiologia , Permeabilidade , Estudos Soroepidemiológicos , Síndrome de Imunodeficiência Adquirida dos Símios/virologia
13.
J Med Primatol ; 48(3): 176-178, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30847920

RESUMO

HIV infection induces pathological changes in the intestinal mucosa. Here, a successful endoscopy was performed on the colon of a Chinese rhesus macaque by using Olympus CV170 gastroscope. The stability on postoperative recovery and the integrity of biopsy tissue implied a possibility of achieving AIDS longitudinal intestinal research on macaques.


Assuntos
Síndrome de Imunodeficiência Adquirida/patologia , Colonoscopia/veterinária , Mucosa Intestinal/diagnóstico por imagem , Macaca mulatta , Animais , Síndrome de Imunodeficiência Adquirida dos Símios/patologia
14.
J Assoc Nurses AIDS Care ; 29(5): 681-697, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29716789

RESUMO

As key population groups in HIV infection, transgender women (TGW) share the same oral and anal sexual practices with men who have sex with men (MSM). However, the differences in HIV rates between the two groups are still unclear. In our study, relevant publications were electronically searched in three databases. After excluding irrelevant studies based on review of the title, abstract, and full text, a total of 24 studies, including 37,521 cases, were identified. There were no significant differences between TGW and MSM regarding HIV status and condom use. However, TGW had a higher proportion of high-risk behaviors, including exchanges of sex, forced sex, receptive intercourse, and sex work experience. Moreover, most curable sexually transmitted diseases were more prevalent in the TGW group compared to MSM. Although TGW showed a higher proportion of high-risk behavior and sexually transmitted disease incidence, their HIV incidence was the same as that for MSM.


Assuntos
Infecções por HIV/epidemiologia , Homossexualidade Masculina , Doenças Sexualmente Transmissíveis/epidemiologia , Transexualidade , Sexo sem Proteção/estatística & dados numéricos , Adulto , Feminino , Infecções por HIV/diagnóstico , Humanos , Masculino , Prevalência , Trabalho Sexual/estatística & dados numéricos , Parceiros Sexuais , Doenças Sexualmente Transmissíveis/diagnóstico , Pessoas Transgênero
15.
Zool Res ; 39(1): 42-51, 2018 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-29511144

RESUMO

Parasites can increase infection rates and pathogenicity in immunocompromised human immunodeficiency virus (HIV) patients. However, in vitro studies and epidemiological investigations also suggest that parasites might escape immunocompromised hosts during HIV infection. Due to the lack of direct evidence from animal experiments, the effects of parasitic infections on immunocompromised hosts remain unclear. Here, we detected 14 different parasites in six northern pig-tailed macaques (NPMs) before or at the 50th week of simian immunodeficiency virus (SIV) infection by ELISA. The NPMs all carried parasites before viral injection. At the 50th week after viral injection, the individuals with negative results in parasitic detection (i.e., 08247 and 08287) were characterized as the Parasites Exit (PE) group, with the other individuals (i.e., 09203, 09211, 10205, and 10225) characterized as the Parasites Remain (PR) group. Compared with the PR group, the NPMs in the PE group showed higher viral loads, lower CD4+ T cells counts, and lower CD4/CD8 rates. Additionally, the PE group had higher immune activation and immune exhaustion of both CD4+ and CD8+ T cells. Pathological observation showed greater injury to the liver, cecum, colon, spleen, and mesenteric lymph nodes in the PE group. This study showed more seriously compromised immunity in the PE group, strongly indicating that parasites might exit an immunocompromised host.


Assuntos
Hospedeiro Imunocomprometido , Macaca/virologia , Doenças Parasitárias em Animais/virologia , Síndrome de Imunodeficiência Adquirida dos Símios/parasitologia , Animais , Linfócitos B/imunologia , Macaca/imunologia , Macaca/parasitologia , Masculino , Monócitos/imunologia , Doenças Parasitárias em Animais/etiologia , Doenças Parasitárias em Animais/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia , Linfócitos T/imunologia , Carga Viral
17.
Immunology ; 152(4): 574-579, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28707699

RESUMO

Macaca leonina (northern pig-tailed macaques, NPMs) have variable disease progression during SIVmac239 infection. In the present study, we analysed, for the first time, the correlations between T-cell phenotypes and disease progression in NPMs during SIVmac239 infection. In comparison to normal progressors (NPs), slow progressors (SPs) had lower chronic T-cell activation and exhaustion levels. In addition, SPs showed higher peripheral CD4+ T-cell count and CD4 : CD8 ratio, and lower plasma viral load than NPs. CD4+ T-cell count and CD4 : CD8 ratio decreased more sharply in NPs than in SPs. Furthermore, T cells in NPs were more highly differentiated, at least in acute infection, than in SPs. These results indicated that T-cell phenotypes were correlated with disease progression in SIVmac239-infected NPMs and these correlations may provide valuable guidance for the improvement of therapeutic strategies tested in NPMs.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/imunologia , Animais , Relação CD4-CD8 , Macaca nemestrina , Masculino
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