resource : emedicine
After HIV enters a host, the trimeric gp120 glycoproteins that protrude from its lipoprotein bilayer envelope bind to CD4 cell surface receptors and CCR5 or CXCR4 chemokine coreceptors. CD4 receptors are located on CD4 T lymphocytes, monocytes, and macrophages, but juxtapositioned coreceptors are also needed for viral infection. The V3 region of the gp120 glycoprotein determines cellular tropism, and tropism is involved in syncytial formation. M-tropic (nonsyncytial) strains prefer the CCR5 coreceptor and are the primary causes of infection. CCR5 chemokine coreceptor deficiency is present in as many as 10% of Europeans and 20% of Ashkenazi Jews, and it appears to confer some protection against infection. Once gp120 binds to the receptors, the associated gp41 transmembrane glycoprotein is inserted into the cell membrane and initiates cell-membrane fusion.
On entering the cell, the protease enzyme produces the reverse transcriptase and ribonuclease (RNAse) H enzymes that are responsible for synthesizing single-stranded DNA (ssDNA) molecules and primers necessary to produce the complementary DNA strand. Because reverse transcriptase lacks proofreading machinery, significant base-to-base variability results. The high mutation rate, combined with the high reproductive rate, results in substantial evolution and subsequent resistance to treatment.
Acute infection rapidly increases the viral load and causes a mild-to-moderate viremia. Although viral loads tend to diminish rapidly after acute infection in adults, viral loads decrease more slowly in vertically infected children and may not reach a baseline level until they are aged 4 or 5 years. Although infants possess a high number of antigen-presenting and effector cells compared with the number in adults, their cytokine production, proliferation, and cytotoxicity are reduced.
Envelope-specific cytotoxic T lymphocytes are much less common in children with vertically acquired disease compared with children who acquire HIV by means of blood transfusion, and, among those with vertically acquired disease, the lymphocytes are less common in those with rapidly progressing disease than in those without rapid progression. Cytotoxic T-lymphocyte precursors specific to HIV type 1 (HIV-1) do not develop in significant number until the child is aged 1 year. In adults, antibodies to gp120 develop several months after the initial viremia. The development of broadly neutralizing antibodies is associated with slower disease progression in adults, children, and infants
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