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HIV-1 co-receptor usage: influence on mother-to-child transmission and pediatric infection.

Cavarelli M, Scarlatti G - J Transl Med (2011)

Bottom Line: The virus phenotype of the infected children, like that of adults, can evolve from R5 to CXCR4-using phenotype or remain R5 despite clinical progression to overt immune deficiency.The refined classification of R5 viruses into R5(narrow) and R5(broad) resolves the enigma of the R5 phenotype being associated with the state of immune deficiency.Studies are needed to address more in specific the relevance of these factors in HIV-1 MTCT and pediatric infection of non-B subtypes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Unit of Viral Evolution and Transmission, Division of Immunology, Transplant and Infectious Diseases, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.

ABSTRACT
Viral CCR5 usage is not a predictive marker of mother to child transmission (MTCT) of HIV-1. CXCR4-using viral variants are little represented in pregnant women, have an increased although not significant risk of transmission and can be eventually also detected in the neonates. Genetic polymorphisms are more frequently of relevance in the child than in the mother. However, specific tissues as the placenta or the intestine, which are involved in the prevalent routes of infection in MTCT, may play an important role of selective barriers. The virus phenotype of the infected children, like that of adults, can evolve from R5 to CXCR4-using phenotype or remain R5 despite clinical progression to overt immune deficiency. The refined classification of R5 viruses into R5(narrow) and R5(broad) resolves the enigma of the R5 phenotype being associated with the state of immune deficiency. Studies are needed to address more in specific the relevance of these factors in HIV-1 MTCT and pediatric infection of non-B subtypes.

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Related in: MedlinePlus

The R5broad phenotype is predictive of early immunological failure in children. Categories are defined according to the Centers for Disease Controls [111]: CDC 3 = severe immune suppression. Narrow and broad refer to viruses with R5 phenotype detected at or close to birth. Viruses able to exclusively use wild type CCR5 receptor are defined narrow, whereas those using chimeric receptors besides the wild type CCR5 are defined broad. Statistical analysis was performed to detect the influence of the virus with R5broad phenotype on disease progression of the children; p = 0.0218 (Pearson’s chi Square).
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Figure 1: The R5broad phenotype is predictive of early immunological failure in children. Categories are defined according to the Centers for Disease Controls [111]: CDC 3 = severe immune suppression. Narrow and broad refer to viruses with R5 phenotype detected at or close to birth. Viruses able to exclusively use wild type CCR5 receptor are defined narrow, whereas those using chimeric receptors besides the wild type CCR5 are defined broad. Statistical analysis was performed to detect the influence of the virus with R5broad phenotype on disease progression of the children; p = 0.0218 (Pearson’s chi Square).

Mentions: Increasing evidences are emerging showing that the classical dichotomy of the viral phenotype into R5 and X4 is not sufficient to explain the large phenotypic variation of HIV-1 [5]. Further classification of R5 viruses into R5narrow and R5broad permitted to explain why some children progress more rapidly than others, despite the early presence of an R5 phenotype close to birth [6]. Our recent study performed on 28 infected newborns demonstrated that the presence of viruses with R5broad phenotype close to birth was significantly associated with a fast progression to severe immunological failure within 3 years of age (Figure 1). Thus, infection in children established by R5broad viral variants with an envelope conformation that allows for a more efficient CCR5 use, determine detrimental effects similar to those known for CXCR4 using viruses. The refined classification of R5 viruses into R5narrow and R5broad resolves the enigma of the R5 phenotype being associated with the state of immune deficiency. These data support the finding by Casper et al. [1], who suggested that the immunological deterioration in HIV-1 infected children precedes the viral phenotypic switch to CXCR4 usage. One could argue that pre-existing R5broad viruses may have caused the worsening of the disease in the cohort analyzed by this study.


HIV-1 co-receptor usage: influence on mother-to-child transmission and pediatric infection.

Cavarelli M, Scarlatti G - J Transl Med (2011)

The R5broad phenotype is predictive of early immunological failure in children. Categories are defined according to the Centers for Disease Controls [111]: CDC 3 = severe immune suppression. Narrow and broad refer to viruses with R5 phenotype detected at or close to birth. Viruses able to exclusively use wild type CCR5 receptor are defined narrow, whereas those using chimeric receptors besides the wild type CCR5 are defined broad. Statistical analysis was performed to detect the influence of the virus with R5broad phenotype on disease progression of the children; p = 0.0218 (Pearson’s chi Square).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105501&req=5

Figure 1: The R5broad phenotype is predictive of early immunological failure in children. Categories are defined according to the Centers for Disease Controls [111]: CDC 3 = severe immune suppression. Narrow and broad refer to viruses with R5 phenotype detected at or close to birth. Viruses able to exclusively use wild type CCR5 receptor are defined narrow, whereas those using chimeric receptors besides the wild type CCR5 are defined broad. Statistical analysis was performed to detect the influence of the virus with R5broad phenotype on disease progression of the children; p = 0.0218 (Pearson’s chi Square).
Mentions: Increasing evidences are emerging showing that the classical dichotomy of the viral phenotype into R5 and X4 is not sufficient to explain the large phenotypic variation of HIV-1 [5]. Further classification of R5 viruses into R5narrow and R5broad permitted to explain why some children progress more rapidly than others, despite the early presence of an R5 phenotype close to birth [6]. Our recent study performed on 28 infected newborns demonstrated that the presence of viruses with R5broad phenotype close to birth was significantly associated with a fast progression to severe immunological failure within 3 years of age (Figure 1). Thus, infection in children established by R5broad viral variants with an envelope conformation that allows for a more efficient CCR5 use, determine detrimental effects similar to those known for CXCR4 using viruses. The refined classification of R5 viruses into R5narrow and R5broad resolves the enigma of the R5 phenotype being associated with the state of immune deficiency. These data support the finding by Casper et al. [1], who suggested that the immunological deterioration in HIV-1 infected children precedes the viral phenotypic switch to CXCR4 usage. One could argue that pre-existing R5broad viruses may have caused the worsening of the disease in the cohort analyzed by this study.

Bottom Line: The virus phenotype of the infected children, like that of adults, can evolve from R5 to CXCR4-using phenotype or remain R5 despite clinical progression to overt immune deficiency.The refined classification of R5 viruses into R5(narrow) and R5(broad) resolves the enigma of the R5 phenotype being associated with the state of immune deficiency.Studies are needed to address more in specific the relevance of these factors in HIV-1 MTCT and pediatric infection of non-B subtypes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Unit of Viral Evolution and Transmission, Division of Immunology, Transplant and Infectious Diseases, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.

ABSTRACT
Viral CCR5 usage is not a predictive marker of mother to child transmission (MTCT) of HIV-1. CXCR4-using viral variants are little represented in pregnant women, have an increased although not significant risk of transmission and can be eventually also detected in the neonates. Genetic polymorphisms are more frequently of relevance in the child than in the mother. However, specific tissues as the placenta or the intestine, which are involved in the prevalent routes of infection in MTCT, may play an important role of selective barriers. The virus phenotype of the infected children, like that of adults, can evolve from R5 to CXCR4-using phenotype or remain R5 despite clinical progression to overt immune deficiency. The refined classification of R5 viruses into R5(narrow) and R5(broad) resolves the enigma of the R5 phenotype being associated with the state of immune deficiency. Studies are needed to address more in specific the relevance of these factors in HIV-1 MTCT and pediatric infection of non-B subtypes.

Show MeSH
Related in: MedlinePlus