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Role of Nucleotide Sequences in the V3 Region in Efficient Replication of CCR5-Utilizing Human Immunodeficiency Virus Type 1 in Macrophages
- Source :
-
Virology . Aug2002, Vol. 299 Issue 2, p192. 12p. - Publication Year :
- 2002
-
Abstract
- Macrophages express both CXCR4 and CCR5 coreceptors, but restrict X4 HIV-1 replication unless the Env-V3 region, a major determinant of cell tropism, is exchanged with that of R5 HIV-1. As the V3 exchange concomitantly alters the nucleotide sequences, we introduced silent mutations in the V3 or C2 region of macrophage-tropic R5 JRFL without changing the amino acids. Immunoblot analysis confirmed that viral proteins including Env-gp120 were similarly incorporated in wild-type (wt) and mutant virions. The silent mutants infected CCR5-positive MAGIC5 cells but not CCR5-negative MAGI cells, as productively as wt viruses, indicating that the silent mutations did not alter coreceptor utilization. In contrast, two of three silent V3-mutant viruses failed to replicate efficiently in primary macrophages, whereas other V3- or C2-mutants and wt JRFL infected macrophages productively. Furthermore, synthesis of the full-length viral DNA of the aberant V3-mutant was largely reduced in macrophages. These results suggest that V3 nucleotide sequences may be one of the postentry factors restricting HIV-1 replication in macrophages. [Copyright &y& Elsevier]
- Subjects :
- *MACROPHAGES
*NUCLEOTIDE sequence
*HIV
Subjects
Details
- Language :
- English
- ISSN :
- 00426822
- Volume :
- 299
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Virology
- Publication Type :
- Academic Journal
- Accession number :
- 8512968
- Full Text :
- https://doi.org/10.1006/viro.2002.1521