scholarly journals miR-223: An Immune Regulator in Infectious Disorders

2021 ◽  
Vol 12 ◽  
Author(s):  
Shun Yuan ◽  
Qi Wu ◽  
Zhiwei Wang ◽  
Yanjia Che ◽  
Sihao Zheng ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Immune Responses ◽  
Noncoding Rnas ◽  
Neutrophil Infiltration ◽  
Inflammasome Activation ◽  
Immunodeficiency Virus ◽  
Regulatory Functions ◽  
Hiv 1 ◽  
Dc Maturation

MicroRNAs (miRNAs) are diminutive noncoding RNAs that can influence disease development and progression by post-transcriptionally regulating gene expression. The anti-inflammatory miRNA, miR-223, was first identified as a regulator of myelopoietic differentiation in 2003. This miR-223 exhibits multiple regulatory functions in the immune response, and abnormal expression of miR-223 is shown to be associated with multiple infectious diseases, including viral hepatitis, human immunodeficiency virus type 1 (HIV-1), and tuberculosis (TB) by influencing neutrophil infiltration, macrophage function, dendritic cell (DC) maturation and inflammasome activation. This review summarizes the current understanding of miR-223 physiopathology and highlights the molecular mechanism by which miR-223 regulates immune responses to infectious diseases and how it may be targeted for diagnosis and treatment.

scholarly journals Induction of Humoral Immune Responses following Vaccination with Envelope-Containing, Formaldehyde-Treated, Thermally Inactivated Human Immunodeficiency Virus Type 1

2005 ◽  
Vol 79 (8) ◽  
pp. 4927-4935 ◽  
Author(s):  
B. Poon ◽  
J. T. Safrit ◽  
H. McClure ◽  
C. Kitchen ◽  
J. F. Hsu ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Thermal Treatment ◽  
Immune Responses ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The lack of success of subunit human immunodeficiency virus type 1 (HIV-1) vaccines to date suggests that multiple components or a complex virion structure may be required. We previously demonstrated retention of the major conformational epitopes of HIV-1 envelope following thermal treatment of virions. Moreover, antibody binding to some of these epitopes was significantly enhanced following thermal treatment. These included the neutralizing epitopes identified by monoclonal antibodies 1b12, 2G12, and 17b, some of which have been postulated to be partially occluded or cryptic in native virions. Based upon this finding, we hypothesized that a killed HIV vaccine could be derived to elicit protective humoral immune responses. Shedding of HIV-1 envelope has been described for some strains of HIV-1 and has been cited as one of the major impediments to developing an inactivated HIV-1 vaccine. In the present study, we demonstrate that treatment of virions with low-dose formaldehyde prior to thermal inactivation retains the association of viral envelope with virions. Moreover, mice and nonhuman primates vaccinated with formaldehyde-treated, thermally inactivated virions produce antibodies capable of neutralizing heterologous strains of HIV in peripheral blood mononuclear cell-, MAGI cell-, and U87-based infectivity assays. These data indicate that it is possible to create an immunogen by using formaldehyde-treated, thermally inactivated HIV-1 virions to induce neutralizing antibodies. These findings have broad implications for vaccine development.

scholarly journals Human Immunodeficiency Virus Type 1-Hepatitis C Virus Coinfection: Intraindividual Comparison of Cellular Immune Responses against Two Persistent Viruses

2002 ◽  
Vol 76 (6) ◽  
pp. 2817-2826 ◽  
Author(s):  
Georg M. Lauer ◽  
Tam N. Nguyen ◽  
Cheryl L. Day ◽  
Gregory K. Robbins ◽  
Theresa Flynn ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
T Lymphocyte ◽  
Viral Loads ◽  
Cellular Immune Responses ◽  
Immunodeficiency Virus ◽  
Cellular Immune ◽  
Lymphocyte Responses ◽  
Hiv 1

ABSTRACT Both human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) lead to chronic infection in a high percentage of persons, and an expanding epidemic of HIV-1-HCV coinfection has recently been identified. These individuals provide an opportunity for simultaneous assessment of immune responses to two viral infections associated with chronic plasma viremia. In this study we analyzed the breadth and magnitude of the CD8+- and CD4+-T-lymphocyte responses in 22 individuals infected with both HIV-1 and HCV. A CD8+-T-lymphocyte response against HIV-1 was readily detected in all subjects over a broad range of viral loads. In marked contrast, HCV-specific CD8+-T-lymphocyte responses were rarely detected, despite viral loads in plasma that were on average 1,000-fold higher. The few HCV-specific responses that were observed were relatively weak and limited in breadth. CD4-proliferative responses against HIV-1 were detected in about half of the coinfected subjects tested, but no proliferative response against any HCV protein was found in these coinfected persons. These data demonstrate a major discordance in immune responses to two persistent RNA viruses. In addition, they show a consistent and profound impairment in cellular immune responses to HCV compared to HIV-1 in HIV-1-HCV-coinfected persons.

scholarly journals A Single Injection of Recombinant Measles Virus Vaccines Expressing Human Immunodeficiency Virus (HIV) Type 1 Clade B Envelope Glycoproteins Induces Neutralizing Antibodies and Cellular Immune Responses to HIV

2004 ◽  
Vol 78 (1) ◽  
pp. 146-157 ◽  
Author(s):  
Clarisse Lorin ◽  
Lucile Mollet ◽  
Frédéric Delebecque ◽  
Chantal Combredet ◽  
Bruno Hurtrel ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Measles Virus ◽  
Single Injection ◽  
Protein A ◽  
V3 Loop ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The anchored and secreted forms of the human immunodeficiency virus type 1 (HIV-1) 89.6 envelope glycoprotein, either complete or after deletion of the V3 loop, were expressed in a cloned attenuated measles virus (MV) vector. The recombinant viruses grew as efficiently as the parental virus and expressed high levels of the HIV protein. Expression was stable during serial passages. The immunogenicity of these recombinant vectors was tested in mice susceptible to MV and in macaques. High titers of antibodies to both MV and HIV-Env were obtained after a single injection in susceptible mice. These antibodies neutralized homologous SHIV89.6p virus, as well as several heterologous HIV-1 primary isolates. A gp160 mutant in which the V3 loop was deleted induced antibodies that neutralized heterologous viruses more efficiently than antibodies induced by the native envelope protein. A high level of CD8+ and CD4+ cells specific for HIV gp120 was also detected in MV-susceptible mice. Furthermore, recombinant MV was able to raise immune responses against HIV in mice and macaques with a preexisting anti-MV immunity. Therefore, recombinant MV vaccines inducing anti-HIV neutralizing antibodies and specific T lymphocytes responses deserve to be tested as a candidate AIDS vaccine.

scholarly journals Mucosal and Systemic Immune Responses to a Human Immunodeficiency Virus Type 1 Epitope Induced upon Vaginal Infection with a Recombinant Influenza A Virus

2004 ◽  
Vol 78 (2) ◽  
pp. 1020-1025 ◽  
Author(s):  
Bruno Garulli ◽  
Yoshihiro Kawaoka ◽  
Maria R. Castrucci
Keyword(s):  
Human Immunodeficiency Virus ◽  
Influenza Virus ◽  
Immune Responses ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Envelope Gene ◽  
Vaginal Infection ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The humoral and cellular immune responses in the genital mucosa likely play an important role in the prevention of sexually transmitted infections, including infection with human immunodeficiency virus type 1 (HIV-1). Here we show that vaginal infection of progesterone-treated BALB/c mice with a recombinant influenza virus bearing the immunodominant P18IIIB cytotoxic T-lymphocyte (CTL) epitope of the gp160 envelope protein from an HIV-1 IIIB isolate (P18IIIB; RIQRGPGRAFVTIGK) can induce a specific immune response in regional mucosal lymph nodes, as well as in a systemic site (the spleen). A single inoculation of mice with the recombinant influenza virus induced long-lasting (at least 5 months) antigen-specific CTL memory detectable as a rapid recall of effector CTLs upon vaginal infection with recombinant vaccinia virus expressing HIV-1 IIIB envelope gene products. Long-term antigen-specific CTL memory was also induced and maintained in distant mucosal tissues when mice were intranasally immunized with the recombinant influenza virus. These results indicate that mucosal immunization and, in particular, local vaginal immunization with recombinant influenza virus can provide strong, durable immune responses in the female genital tract of mice.

scholarly journals Initial B-Cell Responses to Transmitted Human Immunodeficiency Virus Type 1: Virion-Binding Immunoglobulin M (IgM) and IgG Antibodies Followed by Plasma Anti-gp41 Antibodies with Ineffective Control of Initial Viremia

2008 ◽  
Vol 82 (24) ◽  
pp. 12449-12463 ◽  
Author(s):  
Georgia D. Tomaras ◽  
Nicole L. Yates ◽  
Pinghuang Liu ◽  
Li Qin ◽  
Genevieve G. Fouda ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
B Cell ◽  
Human Immunodeficiency Virus Type ◽  
Igg Antibodies ◽  
Plasma Virus ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT A window of opportunity for immune responses to extinguish human immunodeficiency virus type 1 (HIV-1) exists from the moment of transmission through establishment of the latent pool of HIV-1-infected cells. A critical time to study the initial immune responses to the transmitted/founder virus is the eclipse phase of HIV-1 infection (time from transmission to the first appearance of plasma virus), but, to date, this period has been logistically difficult to analyze. To probe B-cell responses immediately following HIV-1 transmission, we have determined envelope-specific antibody responses to autologous and consensus Envs in plasma donors from the United States for whom frequent plasma samples were available at time points immediately before, during, and after HIV-1 plasma viral load (VL) ramp-up in acute infection, and we have modeled the antibody effect on the kinetics of plasma viremia. The first detectable B-cell response was in the form of immune complexes 8 days after plasma virus detection, whereas the first free plasma anti-HIV-1 antibody was to gp41 and appeared 13 days after the appearance of plasma virus. In contrast, envelope gp120-specific antibodies were delayed an additional 14 days. Mathematical modeling of the earliest viral dynamics was performed to determine the impact of antibody on HIV replication in vivo as assessed by plasma VL. Including the initial anti-gp41 immunoglobulin G (IgG), IgM, or both responses in the model did not significantly impact the early dynamics of plasma VL. These results demonstrate that the first IgM and IgG antibodies induced by transmitted HIV-1 are capable of binding virions but have little impact on acute-phase viremia at the timing and magnitude that they occur in natural infection.

scholarly journals Variability and Immunogenicity of Human Immunodeficiency Virus Type 1 p24 Gene Quasispecies

2000 ◽  
Vol 7 (3) ◽  
pp. 377-383 ◽  
Author(s):  
Johanna Iroegbu ◽  
Markus Birk ◽  
Una Lazdina ◽  
Anders Sönnerborg ◽  
Matti Sällberg
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Human Leukocyte ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Despite the conserved nature of the human immunodeficiency virus type 1 (HIV-1) gag gene, multiple quasispecies of the p24 gene coexist in HIV-1-infected patients. We cloned and sequenced 31 p24 genes from four HIV-1-infected patients. The intrapatient homology between the p24 genes ranged from 97.1 to 99.1%, whereas the interpatient homology ranged from 91.5 to 93.8%, suggesting a host-specific evolution. Synonymous and nonsynonymous nucleotide changes were evenly distributed in the p24 gene, with 27 and 28%, respectively, located within host human leukocyte antigen class I recognition sites. This would suggest only a minor influence from the host cytotoxic T-cell response on the evolution of the p24 gene. The importance of minor variations within p24 was analyzed by designing DNA-based immunogens from two distinct p24 quasispecies genes simultaneously derived from one patient. In plasmid-immunizedH-2b , H-2d , andH-2k haplotype mice, a clear influence from the host major histocompatibility complex was noted on the immune responses, fully consistent with those noted when a recombinant p24 protein is used as the immunogen. The two p24 DNA immunogens did not differ in their immunogenicity, indicating that the limited genetic variability (<1%) had little influence on the immune responses.

scholarly journals Differential CD4+ versus CD8+ T-Cell Responses Elicited by Different Poxvirus-Based Human Immunodeficiency Virus Type 1 Vaccine Candidates Provide Comparable Efficacies in Primates

2008 ◽  
Vol 82 (6) ◽  
pp. 2975-2988 ◽  
Author(s):  
Petra Mooij ◽  
Sunita S. Balla-Jhagjhoorsingh ◽  
Gerrit Koopman ◽  
Niels Beenhakker ◽  
Patricia van Haaften ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
T Cell Responses ◽  
Vaccine Candidates ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Poxvirus vectors have proven to be highly effective for boosting immune responses in diverse vaccine settings. Recent reports reveal marked differences in the gene expression of human dendritic cells infected with two leading poxvirus-based human immunodeficiency virus (HIV) vaccine candidates, New York vaccinia virus (NYVAC) and modified vaccinia virus Ankara (MVA). To understand how complex genomic changes in these two vaccine vectors translate into antigen-specific systemic immune responses, we undertook a head-to-head vaccine immunogenicity and efficacy study in the pathogenic HIV type 1 (HIV-1) model of AIDS in Indian rhesus macaques. Differences in the immune responses in outbred animals were not distinguished by enzyme-linked immunospot assays, but differences were distinguished by multiparameter fluorescence-activated cell sorter analysis, revealing a difference between the number of animals with both CD4+ and CD8+ T-cell responses to vaccine inserts (MVA) and those that elicit a dominant CD4+ T-cell response (NYVAC). Remarkably, vector-induced differences in CD4+/CD8+ T-cell immune responses persisted for more than a year after challenge and even accompanied antigenic modulation throughout the control of chronic infection. Importantly, strong preexposure HIV-1/simian immunodeficiency virus-specific CD4+ T-cell responses did not prove deleterious with respect to accelerated disease progression. In contrast, in this setting, animals with strong vaccine-induced polyfunctional CD4+ T-cell responses showed efficacies similar to those with stronger CD8+ T-cell responses.

scholarly journals Selection for Human Immunodeficiency Virus Type 1 Recombinants in a Patient with Rapid Progression to AIDS

2002 ◽  
Vol 76 (21) ◽  
pp. 10674-10684 ◽  
Author(s):  
Shan-Lu Liu ◽  
John E. Mittler ◽  
David C. Nickle ◽  
Thera M. Mulvania ◽  
Daniel Shriner ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Sequence Motif ◽  
V3 Loop ◽  
Subtype B ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Although human immunodeficiency virus type 1 (HIV-1) recombinants have been found with high frequency, little is known about the forces that select for these viruses or their importance to pathogenesis. Here we document the emergence and dynamics of 11 distinct HIV-1 recombinants in a man who was infected with two subtype B HIV-1 strains and progressed rapidly to AIDS without developing substantial cellular or humoral immune responses. Although numerous frequency oscillations were observed, a single recombinant lineage eventually came to dominate the population. Numerical simulations indicate that the successive recombinant forms displaced each other too rapidly to be explained by any simple model of random genetic drift or sampling variation. All of the recombinants, including several resulting from independent recombination events, possessed the same sequence motif in the V3 loop, suggesting intense selection on this segment of the viral envelope protein. The outgrowth of the predominant V3 loop recombinants was not, however, associated with changes in coreceptor utilization. The final variant was instead notable for having lost 3 of 14 potential glycosylation sites. We also observed high ratios of synonymous-to-nonsynonymous nucleotide changes—suggestive of purifying selection—in all viral populations, with particularly high ratios in newly arising recombinants. Our study, therefore, illustrates the unusual and important patterns of viral adaptation that can occur in a patient with weak immune responses. Although it is hard to tease apart cause and effect in a single patient, the correlation with disease progression in this patient suggests that recombination between divergent viruses, with its ability to create chimeras with increased fitness, can accelerate progression to AIDS.

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