HIV/AIDS: Biological aspects
HIV/AIDS: Biological aspects
Yahia BELLOUCHE
Abstract: The emergence of viral infections has established the importance of the immune system to keep the integrity of our bodies against a hostile, full of pathogens environment, AIDS is the best example illustrating this notion with its severe consequences and eventually exposure to death.
Keywords: AIDS, HIV, virus, LTCD4.
Human immunodeficiency Virus (HIV)
Discovered in 1981, due to an unusual consumption rate of a drug used to treat pneumocystis pneumonia, HIV (Human Immunodeficiency Virus) has been identified as a group of retroviruses (2 subtypes: HIV-1 and HIV-2) originating from some non-human primate species from West Africa , as any virus (Infectious agents with the capacity to invade any living cell and alter its genome in order to assure viral replication using this same cell’s resources in a process known as obligate intracellular parasitism), HIV has a rather simple structure (Figure-1-), two single-stranded RNA chains which code for proteins needed in viral cycles and a few complexes of enzymes (rTranscriptase, integrase -whose function will be explained in later sections-) all surrounded by a capsid delimiting the viral core, and a viral envelope of a lipidic nature (Explaining the fragility of viral particles, and their direct mode of transmission), this last, contains a glycoprotein surface antigen complex (gp41/gp120) major factor of HIV’s specific tropism to immunity system elements, other elements exist in between the core and matrix, as it is the case of an enzyme “protease” used in the process of invasion to alter the host cell antiviral complexes, this past description concerns the independent extracellular form, as of the existence of heterogeneous intracellular forms.
As mentioned before, HIV has a particular viral tropism, determined by the specificity of epitopes exposed in its surface. Mainly infected, lymphocytes T CD4+ (LTCD4) are vital elements of specific immune responses (Whose integrity is crucial for its efficiency against the different threats the human body may face), standing in the heart of the immune response regulation process in both the cellular and the humoral pathways (Figure-2- ), any alteration of their function, will lead to a sever condition of vulnerability with opportunistic infections, tumors and organs failure known as AIDS (Acquired Immune Deficiency Syndrome). HIV may infect other cell types such as macrophage and dendritic cells, both altering furthermore the immune function.
The virus transmission
As any conventional transmissible agent, HIV obeys to the classic scheme of transmission: from an infected organism with the sufficient blood viral load, the viral particle is transmitted to the new host to cause the infection primarily, and the state of immunodeficiency later on (after a variable period of time), but the fragile structure of the virus (lipidic envelope mainly) limits its propagation capacity through respiratory, digestive and cutaneous pathways, as a results, the major modes of transmission imply biological bodily fluids, such as blood, genital secretions and breast milk, which can contain both independent and intracellular forms of HIV. Sexual contact (all unprotected practices combined), is by far the main path, with the highest transmission risk (more than half new cases every year), the other ways include uncontrolled blood products accidental or illegal transfers (transfusion, drugs addiction) or any direct contact between a contaminated fluid and the host’s blood, finally, with a low but an important risk of transmission, vertical mode (Mother- child) during pregnancy through placenta or through breastfeeding later on, which indicated the enormous infection potential of these elements, HIV-2 is a less aggressive virus with a lower risk of transmission and AIDS development.
Host cell vs. Virus (Virus cell interaction)
Once in the blood stream, the virus begins right away the process of invasion, facilitated by the complementarity between its surface antigens, and the target cell’s mentioned before, particularly, the viral gp120 and the cell CCR5/CD4, this link activates the rest of steps, fusion of the membranes, lysis of the matrix and the capsid which liberates the countenance of the core to the cytoplasm where the rTranscriptase transform the chains of RNA into DNA chains that can be translocated to the nucleus where they get included in the cell’s genome with the participation of the integrase (enzyme of DNA modification) announcing the end of invasion, the first step in HIV-infected cell natural history (Figure-3-).
Once in the blood stream, the virus begins right away the process of invasion, facilitated by the complementarity between its surface antigens, and the target cell’s mentioned before, particularly, the viral gp120 and the cell CCR5/CD4, this link activates the rest of steps, fusion of the membranes, lysis of the matrix and the capsid which liberates the countenance of the core to the cytoplasm where the rTranscriptase transform the chains of RNA into DNA chains that can be translocated to the nucleus where they get included in the cell’s genome with the participation of the integrase (enzyme of DNA modification) announcing the end of invasion, the first step in HIV-infected cell natural history (Figure-3-).
On the other hand, the scenario described before supposes a defenseless cell, which is far from the reality of things, in a matter of fact, the cell is provided with some proteins with the ability to block fusion, transcription or integration of viral genome inside its own, a set of mechanisms known as intrinsic immunity, so the infection of a cell is the outcome of a conflict between the two parties and the replication begins in an explosive model, causing cell death, by many mechanisms: apoptosis, immune destruction of infected cells by LTCD8 and eventually, exhaustion of resources; With periods of latency in between defining the nosologic entity known as HIV/AIDS.
HIV/AIDS
In the light of contamination, and after treating the microscopic Virus vs. Host conflict, it is only adequate to explain what happens in the macroscopic realm, the spectrum of the signs and symptoms that occur within the period of infection are classically divided into three different stages: Acute infection, clinical latency and AIDS stricto sensu without any obligate chronological sequence (some forms do not express any signs until AIDS).
Acute Infection
Corresponds to the period of massive invasion of immune system cells, two to four weeks following the contamination, the patient may expose a set of nonspecific signs, most experience influenza signs such as fever, headaches and fatigue, others feel some minor signs like a rash, lymph nodes, malaise, night sweats and anorexia, some rare forms in the other hand, may be accompanied with some serious health problems such as diarrhea, and neurological peripheral disorders marking a very poor prognosis and a fast development to AIDS, still, most of cases are exceptionally evocative at this stage.
Clinical latency
With a large duration variability (from two to thirty years), this stage corresponds to the period of chronic infection, clinically latent, no signs are usually noticed, giving a false impression of good health resulting from a fragile equilibrium state between the viral replication rate and the adaptive immune system response.
Acquired immune deficiency syndrome
Ultimately, the virus ends up by destroying the majority of functional immune system cells, which leads to a total meltdown and a body vulnerable to all sorts of endogenous and environmental risks.
Infections are the first to occur, with the particularity of being more expressive and aggressive, and tend to be caused by some unusual “opportunistic” agents considered naturally non-pathogenic, such as pneumocystis, candidiasis and zona. Besides, the absence of immune regulation, permits the accumulation of irregular cells in tissues, which can be later on a ground to cancer clones development, and increasing the risk of cancer occurrence among the AIDS patients, especially, lymphomas (Lymphatic tissue cancers) and sarcomas (connective tissue originating cancers) which are usually very aggressive and impossible to cure.
Finally, the accumulation of all this effects, leads eventually to organs failure and a systemic dysfunction in a domino effect total failure, and so, the inevitable death of the subject.
References:
HIV/AIDS
In the light of contamination, and after treating the microscopic Virus vs. Host conflict, it is only adequate to explain what happens in the macroscopic realm, the spectrum of the signs and symptoms that occur within the period of infection are classically divided into three different stages: Acute infection, clinical latency and AIDS stricto sensu without any obligate chronological sequence (some forms do not express any signs until AIDS).
Acute Infection
Corresponds to the period of massive invasion of immune system cells, two to four weeks following the contamination, the patient may expose a set of nonspecific signs, most experience influenza signs such as fever, headaches and fatigue, others feel some minor signs like a rash, lymph nodes, malaise, night sweats and anorexia, some rare forms in the other hand, may be accompanied with some serious health problems such as diarrhea, and neurological peripheral disorders marking a very poor prognosis and a fast development to AIDS, still, most of cases are exceptionally evocative at this stage.
Clinical latency
With a large duration variability (from two to thirty years), this stage corresponds to the period of chronic infection, clinically latent, no signs are usually noticed, giving a false impression of good health resulting from a fragile equilibrium state between the viral replication rate and the adaptive immune system response.
Acquired immune deficiency syndrome
Ultimately, the virus ends up by destroying the majority of functional immune system cells, which leads to a total meltdown and a body vulnerable to all sorts of endogenous and environmental risks.
Infections are the first to occur, with the particularity of being more expressive and aggressive, and tend to be caused by some unusual “opportunistic” agents considered naturally non-pathogenic, such as pneumocystis, candidiasis and zona. Besides, the absence of immune regulation, permits the accumulation of irregular cells in tissues, which can be later on a ground to cancer clones development, and increasing the risk of cancer occurrence among the AIDS patients, especially, lymphomas (Lymphatic tissue cancers) and sarcomas (connective tissue originating cancers) which are usually very aggressive and impossible to cure.
Finally, the accumulation of all this effects, leads eventually to organs failure and a systemic dysfunction in a domino effect total failure, and so, the inevitable death of the subject.
References:
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- Karageorgos L, Li P, Burrell C. Characterization of HIV replication complexes early after cell-to-cell infection. AIDS Res Hum Retroviruses. 1993 Sep;9(9):817-23.
- Kaufmann, S. H. (2007). The contribution of immunology to the rational design of novel antibacterial vaccines. Nature Reviews Microbiology, 491–504, doi:10.1038/nrmicro1688.
- Kozak SL, Heard JM, Kabat D. Segregation of CD4 and CXCR4 into distinct lipid microdomains in T lymphocytes suggests a mechanism for membrane destabilization by human immunodeficiency virus. J Virol. 2002 Feb;76(4):1802-15.
- Kwon DS, Gregorio G, Bitton N, Hendrickson WA, Littman DR. DC-SIGN-mediated internalization of HIV is required for trans- enhancement of T cell infection. Immunity. 2002 Jan;16(1):135-44.
- Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature. 1998 Jun 18;393(6686):648-59.
- Liao Z, Cimakasky LM, Hampton R, Nguyen DH, Hildreth JE. Lipid rafts and HIV pathogenesis: host membrane cholesterol is required for infection by HIV type 1. AIDS Res Hum Retroviruses. 2001 Jul 20;17(11):1009-19.
- Liu R, Paxton WA, Choe S, Ceradini D, Martin SR, Horuk R, MacDonald ME, Stuhlmann H, Koup RA, Landau NR.
Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell. 1996 Aug 9;86(3):367-77.
- Lu X, Yu H, Liu SH, Brodsky FM, Peterlin BM. Interactions between HIV1 Nef and vacuolar ATPase facilitate the internalization of CD4. Immunity. 1998 May;8(5):647-56.
- Martinson JJ, Chapman NH, Rees DC, Liu YT, Clegg JB. Global distribution of the CCR5 gene 32-basepair deletion. Nat Genet. 1997 May;16(1):100-3.
- Ohagen A, Gabuzda D. Role of Vif in stability of the human immunodeficiency virus type 1 core. J Virol. 2000 Dec;74(23):11055-66.
- Scarlatti G, Tresoldi E, Bjorndal A, Fredriksson R, Colognesi C, Deng HK, Malnati MS, Plebani A, Siccardi AG, Littman DR, Fenyo EM, Lusso P. In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression. Nat Med. 1997 Nov;3(11):1259-65.
-Schaeffer E, Geleziunas R, Greene WC. Human immunodeficiency virus type 1 Nef functions at the level of virus entry by enhancing cytoplasmic delivery of virions. J Virol. 2001 Mar;75(6):2993-3000.
-Takeda M, Pekosz A, Shuck K, Pinto LH, Lamb RA. Influenza a virus M2 ion channel activity is essential for efficient replication in tissue culture. J Virol. 2002 Feb;76(3):1391-9.
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