Evidence for late stage compartmentalization of HIV-1 resistance mutations between lymph node and peripheral blood mononuclear cells.
OBJECTIVE
To determine the overall distribution of drug-resistance mutations to nucleoside reverse transcriptase inhibitors of HIV strains recovered from the lymph nodes (LN) and peripheral blood mononuclear cell (PBMC) compartments of four HIV-infected patients receiving zidovudine and didanosine and to compare them with antiretroviral-naive patients.


METHODS
Molecular comparison of major and minor HIV-1 env and pol region variants residing in LN and PBMC compartments.


METHODS
Proviral DNA sequences were amplified by PCR from both PBMC and LN compartments, cloned into PGEM-T II Easy vector and sequenced. The clones were subjected to molecular and phylogenetic analysis.


RESULTS
Comparison of PBMC and LN-derived HIV-1 variants in the env V3 region showed that nucleotide and amino acid variability was a characteristic feature of LN-derived variants. In contrast, a majority of resistance mutations to reverse transcriptase inhibitors were localized in the PBMC compartment rather than in LN, which is thought to be a reservoir of HIV.


CONCLUSIONS
Distinct compartmentalization or independent evolution of pol and env gene variants between LN and PBMC could be due to the differential selection pressure imposed by the combination drug regimen, hence the bimodal distribution of resistance variants between LN and PBMC compartments.
Haddad
D N
DN
Retroviral Genetics Laboratory, Center for Virus Research, Westmead Millennium Institutes, Westmead Hospital, NSW, Sydney, Australia.
Birch
C
C
Middleton
T
T
Dwyer
D E
DE
Cunningham
A L
AL
Saksena
N K
NK
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D016049:Didanosine / Q000627:therapeutic use; D004352:Drug Resistance, Microbial / Q000235:genetics; D019143:Evolution, Molecular; D015752:Genes, env; D015751:Genes, pol; D014644:Genetic Variation; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008198:Lymph Nodes / Q000821:virology*; D008297:Male; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics; D013997:Time Factors; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D015215:Zidovudine; D016049:Didanosine