Replication of human immunodeficiency virus
المؤلف:
Baijayantimala Mishra
المصدر:
Textbook of Medical Virology
الجزء والصفحة:
2nd Edition , p251-252
2025-12-02
11
Receptors and Co-receptors HIV replication begins with binding of envelop glycoprotein gp120 to CD4 (expressed mainly on T lymphocytes, also on monocyte, macrophage, dendritic cells and Langerhans cells). Subsequent to this binding, there occurs a conformational change in gp120 which facilitates binding to other co-receptors, e.g. either C-C chemokine receptor R5 (CCR5) or co-receptor X4 (CXCR4). CXCR4 binding occurs with T cell tropic and syncytium inducing viruses, whereas macrophage tropic viruses bind through CCR5 and are non-syncytium inducing. Depending on the co-receptor used by the virus, it may be either a R5—CCR5 tropic virus or X4—CXCR4 tropic virus.
Subsequent to binding with suitable receptor and co-receptors, newly exposed transmembrane gp41 promotes fusion with the host cell membrane. After fusion with the host cell, the pre-integration complex (comprising of viral RNA, enzymes, accessory proteins, capsid and matrix proteins) traverses through the host cell cytoplasm to reach the nucleus. The viral reverse transcriptase enzyme catalyzes the reverse transcription of genomic RNA into DNA. The HIV hallmark reverse transcriptase enzyme possesses three distinct functions: RNA-dependent DNA polymerase, which facilitates synthesis of complementary DNA (cDNA); ribonuclease H (RNase H), which degrades viral RNA from the cDNA–RNA complex; and a DNA-dependent DNA polymerase, which synthesizes a DNA strand complementary to the cDNA. During the pre-integration and reverse transcription steps, the pre-integration complex is vulnerable to several host proteins like TRIM5a (cytoplasmic tripartite motif containing protein 5a) and apolipoprotein B mRNA editing enzyme (catalytic polypeptide-like 3 [APOBEC3]). After the synthesis of genomic double-stranded DNA, it is integrated with the host cell chromosome via the viral integrase. The integrated HIV DNA genome is called the provirus, which can remain in a latent phase (transcriptionally inactive) for long periods. Subsequent transcription of provirus is dependent upon both cellular activation as well as viral regulatory proteins (tat, rev, nef and vpu). At the end of the replication cycle, assembly of HIV proteins, enzymes, and genomic RNA results in the formation of the virion which buds through the lipid bilayer of the host cell membrane and during budding acquires its external envelop. Host restriction factor tetherin inhibits this budding process. Figure 1 schematically depicts the various steps of HIV1 replication cycle. The functions of the various proteins during replication are summarized in Table 1.
Fig1. H1V1 replication cycle
Table1. Summary of important functions of HIV viral proteins
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