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.
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.
Authors: Natalie N Kinloch; Daniel R MacMillan; Anh Q Le; Laura A Cotton; David R Bangsberg; Susan Buchbinder; Mary Carrington; Jonathan Fuchs; P Richard Harrigan; Beryl Koblin; Margot Kushel; Martin Markowitz; Kenneth Mayer; M J Milloy; Martin T Schechter; Theresa Wagner; Bruce D Walker; Jonathan M Carlson; Art F Y Poon; Zabrina L Brumme Journal: J Virol Date: 2015-11-11 Impact factor: 5.103
Authors: Awet Abraha; Immaculate L Nankya; Richard Gibson; Korey Demers; Denis M Tebit; Elizabeth Johnston; David Katzenstein; Asna Siddiqui; Carolina Herrera; Lucia Fischetti; Robin J Shattock; Eric J Arts Journal: J Virol Date: 2009-03-18 Impact factor: 5.103
Authors: Tasha Biesinger; Robert White; Monica T Yu Kimata; Brenda K Wilson; Jonathan S Allan; Jason T Kimata Journal: Retrovirology Date: 2010-10-13 Impact factor: 4.602
Authors: Samuel Alizon; Viktor von Wyl; Tanja Stadler; Roger D Kouyos; Sabine Yerly; Bernard Hirschel; Jürg Böni; Cyril Shah; Thomas Klimkait; Hansjakob Furrer; Andri Rauch; Pietro L Vernazza; Enos Bernasconi; Manuel Battegay; Philippe Bürgisser; Amalio Telenti; Huldrych F Günthard; Sebastian Bonhoeffer Journal: PLoS Pathog Date: 2010-09-30 Impact factor: 6.823
Authors: Luuk Gras; Suzanne Jurriaans; Margreet Bakker; Ard van Sighem; Daniela Bezemer; Christophe Fraser; Joep Lange; Jan M Prins; Ben Berkhout; Frank de Wolf Journal: PLoS One Date: 2009-10-07 Impact factor: 3.240