Virus phenotype variability during disease progression of HIV-1 infected children

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Retrovirology
Open Access
Oral presentation
Virus phenotype variability during disease progression of HIV-1
infected children
Mariangela Cavarelli*1, Stefania Dispinseri1, Chiara Ripamonti1,
Ingrid Karlsson2, Liselotte Antonsson3, Anna Plebani4, Eva-Maria Fenyö2 and
Gabriella Scarlatti1
Address: 1Viral Evolution and Transmission Unit, DIBIT, HSR, Milan 20132, Italy, 2Division of Medical Microbiology/Virology, Department of
Laboratory Medicine, Lund University, Lund, Sweden, 3Division of Cellular and Molecular Pharmacology, Department of Experimental Medical
Science, Lund University, Lund 223 62, Sweden and 4Department of Pediatrics, University of Milan, Clinica de Marchi, Milan 20122, Italy
* Corresponding author
Background
HIV-1 infected children display different clinical evolu-
tion, i.e., “fast progression” (FP), “slow progression” (SP)
and “long term non progression” (LTNP). One important
phenotypic trait linked to disease progression is the evo-
lution of the viral co-receptor use [1], involving a change
from CCR5 to CXCR4 use [2]. However, AIDS symptoms
can appear in absence of X4 viruses. Recently chimeric
receptors between CCR5 and CXCR4 were developed, in
which subsequent parts of CCR5 were replaced with cor-
responding parts of CXCR4 [3]. Their use allowed to doc-
ument the biological variability of R5 isolates during the
pathogenic process in adults [4].
Aim
To examine the HIV biological variability in children with
different modes of disease progression.
Materials and methods
119 isolates from19 HIV-1 positive children were tested
for their ability to infect U87.CD4+ cells expressing the
wild type receptor CCR5, CXCR4, or one of the 6 chimeric
CCR5/CXCR4 receptors.
Results
Early during infection, all the viruses isolated from 8 SP
children used only wild type CCR5 (called R5narrow). In
one case, this phenotype persisted during disease progres-
sion, whereas in 2 children the virus evolved and was able
to use multiple chimeric receptors (called R5broad), and in
additional 5 children the virus evolved to CXCR4 usage.
Interestengly the FP children, carried close to birth in 2
cases R5narrow virus, in 2 cases R5broad and in one case a
dualtropic R5X4 virus. Virus with R5narrow evolved to
R5broad in one of the 2 children carrying such phenotype.
Both children with R5broad phenotype developed CXCR4
variants during the follow-up.
Evolution was observed also in the LTNP, although fol-
lowed from later on in life (>8 years of age): all tested iso-
lates from 2/6 LTNP remained R5narrow during disease
progression; in one child an evolution from R5narrow to
R5broad was observed whereas in another child the virus
evolved from R5narrow to R5X4. The remaining two chil-
dren showed R5broad phenotype during the whole follow-
up.
Conclusions
Our results show that HIV-1 with broad chimeric receptor
use is not hampered in transmission, and is more frequent
close to birth in FP than in SP children. Viruses from LTNP
show a similar phenotypic evolution though at later age.
from Fourth Dominique Dormont International Conference. Host-Pathogen Interactions in Chronic Infections
Paris, France. 13-15 December 2007
Published: 9 April 2008
Retrovirology 2008, 5(Suppl 1):O28doi:10.1186/1742-4690-5-S1-O28
<supplement> <title> <p>Maternal chronic viral infections transmitted to infants: from mechanisms to prevention and care</p> </title> <note>Meeting abstracts - A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-5-S1-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1742-4690-5-S1-info.pdf</url> </supplement>
This abstract is available from: http://www.retrovirology.com/content/5/S1/O28
© 2008 Cavarelli et al.; licensee BioMed Central Ltd.

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