Replicative fitness of historical and recent HIV-1 isolates suggests HIV-1 attenuation over time.
BACKGROUND
Changes in virulence during an epidemic are common among pathogens, but still unexplored in the case of HIV-1. Here we used primary human cells to study the replicative fitness of primary HIV-1 isolates from untreated patients, comparing historical (1986-1989) and recent samples (2002-2003).


METHODS
Head-to-head dual virus infection/competition assays were performed in both peripheral blood mononuclear cells and human dendritic cell/T-cell co-cultures with pairs of 12 carefully matched historical and recent HIV-1 isolates from untreated patients. Sensitivity to inhibition by lamivudine (3TC) and TAK-779 of historical and recent R5 HIV-1 isolates was measured in a subset of samples.


RESULTS
Overall, the historical HIV-1 out-competed the recent HIV-1 isolates in 176 of 238 competitions and in 9 of 12 competitions carefully matched for CD4 cell count. The mean relative replicative fitness (W) of all historical HIV-1 strains was significantly greater than that of recent HIV-1 isolates (W(1986-1989) = 1.395 and W(2002-2003) = 0.545, P < 0.001 (t test)). The more fit viruses (mean W > 1) from 1986-1989 appeared less sensitive to TAK-779 and 3TC than did the less fit (mean W < 1) 2002-2003 viruses.


CONCLUSIONS
These findings suggest that HIV-1 replicative fitness may have decreased in the human population since the start of the pandemic. This 'attenuation' could be the consequence of serial bottlenecks during transmission and result in adaptation of HIV-1 to the human host.
Ariën
Kevin K
KK
Department of Microbiology, HIV and Retrovirology Research Unit, Institute of Tropical Medicine, Antwerp, Belgium. karien@itg.be
Troyer
Ryan M
RM
Gali
Youssef
Y
Colebunders
Robert L
RL
Arts
Eric J
EJ
Vanham
Guido
G
D000577:Amides / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000821:virology; D015658:HIV Infections / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000821:virology; D008826:Microbial Sensitivity Tests; D010802:Phylogeny; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D019562:Viral Load; D014774:Virulence; D014779:Virus Replication
D000577:Amides; D019380:Anti-HIV Agents; D000644:Quaternary Ammonium Compounds; D019259:Lamivudine; C119369:TAK 779