HIV/AIDS
Patricia G. Melloy in Viruses and Society, 2023
HIV is a retrovirus. Humans are born with what are known as “endogenous retroviruses” in their genome, in addition to possibly acquiring “exogenous retroviruses” like human T-cell leukemia virus (HTLV) and HIV during their lifetimes. Endogenous retroviruses include fragments or whole retroviruses that embedded in our DNA during human evolution and rarely cause disease (Cloyd 1996). HIV is in the Lentivirus genus, a type of enveloped retrovirus that uses reverse transcriptase to make a DNA copy of its genome that then inserts into the host cell genome (Zimmer 2011; Lostroh 2019; Cloyd 1996). Lentiviruses are known for causing chronic infections with a long incubation period, primarily attacking the immune system or the nervous system (Tang, Kuhen, and Wong-Staal 1999; Cruse and Lewis 2009). Lentiviruses are of the Baltimore classification Class VI, which is a single-stranded RNA virus that uses a DNA intermediate for replication (Baltimore 1971). Lentiviruses possess the three critical genes found in any retrovirus: gag, pol, and env, which are necessary for making the structural proteins and enzymes required by the virus (Tang, Kuhen, and Wong-Staal 1999).
The Lymphatic/Immune System and Its Disorders
Walter F. Stanaszek, Mary J. Stanaszek, Robert J. Holt, Steven Strauss in Understanding Medical Terms, 2020
Infection with human immunodeficiency virus (HIV) presents special problems. HIV is a retrovirus that preferentially attacks the T-helper lymphocytes, entering the host cell by attaching at the CD4' site. By reproducing within the T-lymphocytes, HIV kills the host cell and destroys the host's immune response. HIV infection may be asymptomatic, or it may progress to minor or severe immunodeficiency. The severe form is acquired immune deficiency syndrome (AIDS), from which fatality may result because of opportunistic infections. Among the more prominent of the HIV opportunistic infections are Pneumocystis carinii pneumonia, Cytomegalovirus pneumonia, candidiasis, toxoplasmosis, and Herpesvirus infections.
Transplantation
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie in Bailey & Love's Short Practice of Surgery, 2018
The demand for human organs for transplantation is so great that deceased donors can never satisfy it. Many consider that the solution is to perfect xenotransplantation, and there is general agreement that the pig is the most suitable source of xenogeneic organs. However, all humans have preformed antibodies directed against carbohydrate antigens expressed by pig organs, and these cause hyperacute rejection. The dominant carbohydrate antigen responsible is gal-1, 3α-gal. Progress has been made towards circumventing hyperacute xenograft rejection and pigs that have been genetically engineered not to express the gal-1, 3α-gal antigen have been produced. However, organs from genetically modified pigs are still rejected within a few weeks by primates, despite the use of potent immunosuppressive agents. In addition to the complex immunological problems posed by xenotransplantation, there is a risk that pig organs may transmit infectious agents, and there is particular concern about the risks posed by the porcine endogenous retrovirus (PERV). Last, there are unanswered questions about the extent to which pig organs are able to fulfil the physiological demands required of them after transplantation into a human.
Recent advances in nanoformulation development of Ritonavir, a key protease inhibitor used in the treatment of HIV-AIDS
Published in Expert Opinion on Drug Delivery, 2022
Srinivas Reddy Jitta, Navya Ajitkumar Bhaskaran, Shirleen Miriam Marques, Lalit Kumar
Acquired immunodeficiency syndrome (AIDS) is one of the serious healthcare problems causing significant mortality and morbidity globally [1]. AIDS was first recognized in 1981 and is caused by the human immunodeficiency virus (HIV) [2]. HIV is a retrovirus belonging to the genus Lentivirus subfamily of Orthoretrovirinae within the family of Retroviridae. According to global HIV and AIDS statistics 2020, approximately 37.6 million people were living with HIV at the end of 2020. In 2020, 690,000 people died because of HIV-related issues, and 1.5 million were newly infected. As per the statistics, only 27.4 million people received antiretroviral therapy in 2020. Only 53% of children living with HIV received antiretroviral therapy (ART) in 2020. WHO has recommended that all people infected with HIV, including children, adolescents, adults, and pregnant and breastfeeding women, be provided with lifelong ART treatment irrespective of clinical status or CD4 cell count [3]. Even though the death rate fell in the past two decades, people on HIV treatment are still suffering from several adverse effects of antiretroviral therapy. It is one of the main reasons for the lack of adherence to the treatment by HIV patients.
Vitamin D in Prevention and Treatment of COVID-19: Current Perspective and Future Prospects
Published in Journal of the American College of Nutrition, 2021
Navya Vyas, Shilia Jacob Kurian, Debasis Bagchi, Mohan K. Manu, Kavitha Saravu, Mazhuvancherry Kesavan Unnikrishnan, Chiranjay Mukhopadhyay, Mahadev Rao, Sonal Sekhar Miraj
The potent antiviral effect of AMPs has been steadily gaining prominence. Indeed, potential antiviral effects of hCAP18 and hBD have been amply demonstrated against multiple viral infections such as human immunodeficiency virus (HIV)-1, vaccinia virus, herpes simplex virus (HSV)-1 and 2, influenza virus (IFV), rhinovirus (RV), adenovirus (AV) and hepatitis C virus (HCV), etc. A recent clinical trial showed that mega-doses of vitamin D as adjuvant therapy attenuated immune activation and exhaustion caused by antiretroviral treatment for HIV (33). An in vitro study reported a repressive effect of vitamin D on RV replication, possibly by induction of the hCAP18 in primary bronchial epithelial cells from cystic fibrosis patients (34). Vitamin D supplementation has already demonstrated reduced the risk of infection and mortality in influenza and COVID-19 in humans (35). A meta-analysis reported lower serum vitamin D in chronic hepatitis B virus (HBV) patients. Vitamin D levels were inversely correlated with HBV loads (36). Mounting evidence shows that VDD is a risk factor for HCV infections, while vitamin D supplements prevent liver disease progression and enhance response to therapy in HCV patients (37). Likewise, a meta-analysis reported that VDD might increase the likelihood of infection with enveloped viruses, including retrovirus, hepatitis, dengue, and respiratory syncytial virus, etc (38).
Tumor regression and immunity in combination therapy with anti-CEA chimeric antigen receptor T cells and anti-CEA-IL2 immunocytokine
Published in OncoImmunology, 2021
Seung E. Cha, Maciej Kujawski, Paul J. Yazaki, Christine Brown, John E. Shively
On Day 0, 24 well plates pre-coated with 20 µg/well retronectin (Takara, T100B) were incubated overnight at 4°C, per manufacturer’s directions. On Day 1, the activated CD3+ cells with Dynabeads Mouse T-Activator CD3/CD28 were infected in retronectin pre-coated 24 wells plate with retrovirus containing mCD19t (mock T cells) or anti-CEA CAR. Recombinant mouse IL7 (10 ng/mL), recombinant mouse IL2 (50 IU/mL), and β-mercaptoethanol (5.5 mM) were added to retrovirus before transducing CD3+ cells. The MOI was 0.5. The transduced CD3+ cells were incubated overnight at 37°C. On Day 2, retrovirus was removed from each well and replaced with fresh culture media of RPMI 1640 with 10% FBS, 2 mM L-glutamine, antibiotic-antimycotic solution, recombinant mouse IL7, recombinant mouse IL2, and β-mercaptoethanol and plated at 0.5 × 106 cells/well in 24 wells plate overnight. On Day 4, transduced CD3+ cells were collected. The Dynabeads Mouse T-Activator CD3/CD28 were removed from collected transduced CD3+ cells (StemCell, 18000). Truncated mouse CD19-positive CD3+ cells were positively selected using mouse CD19 Positive Selection Kit II (StemCell, 18954), per manufacturer’s directions, and plated at 0.5 × 106 cells/well in 24 wells plate overnight. On Day 5, truncated mouse CD19-positive CD3+ cells were collected and resuspended into 1 × 106 cells/mL concentration for in vitro experiments and 2.5 × 107 cells/mL concentration for in vivo experiments.