Establishment of Chronic and Persistent HIV Infection
المؤلف:
Baijayantimala Mishra
المصدر:
Textbook of Medical Virology
الجزء والصفحة:
2nd Edition , p255-256
2025-12-06
76
Despite the development of strong cellular as well as humoral immune response (as described above in immunopathogenesis subheading) following primary HIV infection, HIV escapes immune mediated clearance and is able to establish a chronic persistent type of infection which is the hallmark of HIV disease. HIV accomplishes this immune evasion primarily by generating viral diversity via mutation and recombination. The resulting quasi-species escapes recognition from cytotoxic T lymphocytes. Furthermore, viral proteins nef, tat, and vpu downregulate HLA class I molecules on the surface of HIV infected cells, which in turn makes the CD8+ CTL unable to recognize and kill the infected target cell.
Several mechanisms are proposed for dysfunction of CD4+ T cells including direct infection and subsequent destruction by HIV, as well as indirect effects, such as immune clearance of infected cells, and immune exhaustion due to aberrant cellular activation.
The following strategies are employed by HIV to evade neutralizing responses directed at the envelop glycoproteins: (i) Hypervariability in the primary sequence of the envelop, (ii) extensive glycosylation of the envelop, and (iii) conformational masking of neutralizing epitopes.
Thus, the evasion of cellular as well humoral arm of immune response constitutes a pool of latently infected cells (also described as post-integration latency) which serve as a reservoir of chronic persistent infection. The viral load gets stabilized when the immune system develops specific cytotoxic T cells against HIV. This point is reached after the acute phase of infection which takes approximately one year from the acquisition of HIV infection. The stabilized viral load achieved at this stage is called “viral set point” which is known to influence the subsequent progression to AIDS in untreated individuals.
In a small subgroup of HIV infected individuals (approx. 5–15%), even after 10 years of primary HIV infection, CD4 T cell counts remain in the normal range and they remain clinically stable without combination ART (cART or combined antiretroviral therapy). They were referred to as “long-term nonprogressors.” However, on long-term follow-up, it has been observed that majority of the long-term non-progressors ultimately develops symptoms and require antiretroviral therapy.
A very small percentage of this group of long-term non-progressors, however, continue to maintain very low plasma viremia (<50 copies/mL plasma) with normal CD4 T cell counts. This group accounts for £1% of HIV infected individuals and are referred to as ‘elite controllers’. The host genetic factors, such as HLA type, heterozygosity for 32-bp deletion in chemokine receptor CCR5, mannose-binding lectin alleles, tumor necrosis factor c2 microsatellite alleles, Gc vitamin D binding factor alleles have been proposed to be the primary factors responsible for elite controller status. Effective immunologic control of virus replication, and/or infection with an attenuated strain of HIV also has been considered as the attributing factors.
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