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The human immunodeficiency viruses (HIV) are two species of Lentivirus that infect humans. Over time,they cause acquired immunodeficiency syndrome (AIDS),a condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment,the average survival time after infection with HIV is estimated to be 9 to 11 years,depending on the HIV subtype.
The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multiple drugs that act on different viral targets is known as highly active antiretroviral therapy (HAART). HAART decreases the patient's total burden of HIV,maintains function of the immune system,and prevents opportunistic infections that often lead to death. HAART also prevents the transmission of HIV between serodiscordant same-sex and opposite-sex partners so long as the HIV-positive partner maintains an undetectable viral load.
Simian immunodeficiency virus (SIV) is a species of retrovirus that cause persistent infections in at least 45 species of non-human primates. Based on analysis of strains found in four species of monkeys from Bioko Island,which was isolated from the mainland by rising sea levels about 11,000 years ago,it has been concluded that SIV has been present in monkeys and apes for at least 32,000 years,and probably much longer.
Feline immunodeficiency virus (FIV) is a Lentivirus that affects cats worldwide,with 2.5% to 4.4% of felines being infected.
Envelope glycoprotein GP120 is a glycoprotein exposed on the surface of the HIV envelope. It was discovered by Professors Tun-Hou Lee and Myron "Max" Essex of the Harvard School of Public Health in 1984. The 120 in its name comes from its molecular weight of 120 kDa. Gp120 is essential for virus entry into cells as it plays a vital role in attachment to specific cell surface receptors. These receptors are DC-SIGN,Heparan Sulfate Proteoglycan and a specific interaction with the CD4 receptor,particularly on helper T-cells. Binding to CD4 induces the start of a cascade of conformational changes in gp120 and gp41 that lead to the fusion of the viral membrane with the host cell membrane. Binding to CD4 is mainly electrostatic although there are van der Waals interactions and hydrogen bonds.
Entry inhibitors,also known as fusion inhibitors,are a class of antiviral drugs that prevent a virus from entering a cell,for example,by blocking a receptor. Entry inhibitors are used to treat conditions such as HIV and hepatitis D.
HIV superinfection is a condition in which a person with an established human immunodeficiency virus infection acquires a second strain of HIV,often of a different subtype. These can form a recombinant strain that co-exists with the strain from the initial infection,as well from reinfection with a new virus strain,and may cause more rapid disease progression or carry multiple resistances to certain HIV medications.
Env is a viral gene that encodes the protein forming the viral envelope. The expression of the env gene enables retroviruses to target and attach to specific cell types,and to infiltrate the target cell membrane.
Antibody-dependent enhancement (ADE),sometimes less precisely called immune enhancement or disease enhancement,is a phenomenon in which binding of a virus to suboptimal antibodies enhances its entry into host cells,followed by its replication. The suboptimal antibodies can result from natural infection or from vaccination. ADE may cause enhanced respiratory disease,but is not limited to respiratory disease. It has been observed in HIV,RSV,and Dengue virus and is monitored for in vaccine development.
Lawrence Corey is an American immunologist and virologist known for his work in the development of antiviral therapies and vaccines,particularly for herpes simplex virus (HSV) and HIV/AIDS.
Long-term nonprogressors (LTNPs),are individuals infected with HIV,who maintain a CD4 count greater than 500 without antiretroviral therapy with a detectable viral load. Many of these patients have been HIV positive for 30 years without progressing to the point of needing to take medication in order not to develop AIDS. They have been the subject of a great deal of research,since an understanding of their ability to control HIV infection may lead to the development of immune therapies or a therapeutic vaccine. The classification "Long-term non-progressor" is not permanent,because some patients in this category have gone on to develop AIDS.
2F5 is a broadly neutralizing human monoclonal antibody (mAb) that has been shown to bind to and neutralize HIV-1 in vitro, making it a potential candidate for use in vaccine synthesis. 2F5 recognizes an epitope in the membrane-proximal external region (MPER) of HIV-1 gp41. 2F5 then binds to this epitope and its constant region interacts with the viral lipid membrane,which neutralizes the virus.
A neutralizing antibody (NAb) is an antibody that defends a cell from a pathogen or infectious particle by neutralizing any effect it has biologically. Neutralization renders the particle no longer infectious or pathogenic. Neutralizing antibodies are part of the humoral response of the adaptive immune system against viruses,bacteria and microbial toxin. By binding specifically to surface structures (antigen) on an infectious particle,neutralizing antibodies prevent the particle from interacting with its host cells it might infect and destroy.
Arthur J. Ammann was an American pediatric immunologist and advocate known for his research on HIV transmission,discovering in utero transmission and the risk of contaminated transfusions and blood products,and his role in the development of the first successful vaccine to prevent pneumococcal infection in 1977. He founded Global Strategies for HIV Prevention and was Clinical Professor of Pediatrics at the UCSF Medical Center.
HIV in pregnancy is the presence of an HIV/AIDS infection in a woman while she is pregnant. There is a risk of HIV transmission from mother to child in three primary situations:pregnancy,childbirth,and while breastfeeding. This topic is important because the risk of viral transmission can be significantly reduced with appropriate medical intervention,and without treatment HIV/AIDS can cause significant illness and death in both the mother and child. This is exemplified by data from The Centers for Disease Control (CDC):In the United States and Puerto Rico between the years of 2014–2017,where prenatal care is generally accessible,there were 10,257 infants in the United States and Puerto Rico who were exposed to a maternal HIV infection in utero who did not become infected and 244 exposed infants who did become infected.
M. Juliana "Julie" McElrath is a senior vice president and director of the vaccine and infection disease division at Fred Hutchinson Cancer Research Center and the principal investigator of the HIV Vaccine Trials Network Laboratory Center in Seattle,Washington. She is also a professor at the University of Washington.
Susan Zolla-Pazner is an American research scientist who is a Professor of Medicine in the Division of Infectious Diseases and the Department of Microbiology at Mount Sinai School of Medicine and a guest investigator in the Laboratory of Molecular Immunology at The Rockefeller University,both in New York City. Zolla-Pazner's work has focused on how the immune system responds to the human immunodeficiency virus (HIV) and,in particular,how antibodies against the viral envelope develop in the course of infection.
Bette Korber is an American computational biologist focusing on the molecular biology and population genetics of the HIV virus that causes infection and eventually AIDS. She has contributed heavily to efforts to obtain an effective HIV vaccine. She created a database at Los Alamos National Laboratory that has enabled her to design novel mosaic HIV vaccines,one of which is currently in human testing in Africa. The database contains thousands of HIV genome sequences and related data.
Karithi Ruth Wanjiru Nduati is a Kenyan Pediatrician and Epidemiologist who also teaches at the University of Nairobi College of Health Sciences. She is also currently leading an interdisciplinary program through the University of Nairobi School of Medicine to educate physician-researchers to best implement HIV treatment and prevention methods backed by research. The program was funded by the Fogarty Training Grant which is a part of the PEPFAR funds the country of Kenya received.
Catherine Blish is a translational immunologist and professor at Stanford University. Her lab works on clinical immunology and focuses primarily on the role of the innate immune system in fighting infectious diseases like HIV,dengue fever,and influenza. Her immune cell biology work characterizes the biology and action of Natural Killer (NK) cells and macrophages.
References
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- ↑ Doepker LE, Danon S, Harkins E, Ralph D, Yaffe Z, Dhar Amrit, Wagner C, Stumpf M, Arenz A, Williams JA, Lee KK, Matsen FA, Overbaugh J. Development of antibody-dependent cell cytotoxicity function in HIV-1 antibodies. Elife. 10: e63444, 2021.
- ↑ Simonich C, Doepker L, Duncan R, Williams JA, Dhar A, Yaffe Z, Gentles L, Small CT, Oliver B, Vigdorovich V, Prasad VM, Nduati R, Sather DN, Lee KK, Matsen FA, Overbaugh J. Kappa chain maturation helps drive rapid development of an infant HIV-1 broadly neutralizing antibody lineage. Nat Commu. 10(1): 2190, 2019.
- ↑ Garrett, M. E.; Galloway, J.; Chu, H. Y.; Itell, H. L.; Stoddard, C. I.; Wolf, C. R.; Logue, J. K.; McDonald, D.; Matsen Fa, 4th; Overbaugh, J. (November 16, 2020). "High-resolution profiling of pathways of escape for SARS-CoV-2 spike-binding antibodies". Cell . 184 (11): 2927–2938. bioRxiv 10.1101/2020.11.16.385278 . doi:10.1016/j.cell.2021.04.045. PMC 7685320 . PMID 33236010.
{{cite journal}}: CS1 maint: numeric names: authors list (link) - ↑ Overbaugh J. Understanding protection from SARS-CoV-2 reinfection. Nature Med. 26(11): 1680-1681, 2020.
- ↑ Gobillot, T. A.; Kikawa, C.; Lehman, D. A.; Kinuthia, J.; Drake, A. L.; Jaoko, W.; Mandaliya, K.; John-Stewart, G.; McClelland, R. S.; Overbaugh, J. (August 4, 2020). "Zika virus circulates at low levels in Western and Coastal Kenya". The Journal of Infectious Diseases . 222 (5): 847–852. doi:10.1093/infdis/jiaa158. PMC 7399697 . PMID 32242626.
- ↑ Sharma A, McLaughlin RN, Basom RS, OhAinle M, Kikawa C, Yount JS, Emerman M, Overbugh J. Macaque interferon-induced transmembrane proteins limit replication of SHIV strains in an Envelope-dependent manner. PLoS Pathog. 15(7): e1007925, 2019.
- ↑ Gobillot T, Humes D, Sharma A, Kikawa C, Overbaugh J. The robust restriction of Zika virus by type-I Interferon in A549 cells varies by viral lineage and is not determined by IFITM3. Viruses. 12(5): 503, 2020.
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