TY - JOUR
T1 - Cell-associated viral burden provides evidence of ongoing viral replication in aviremic HIV-2-infected patients
AU - Soares, Rui S.
AU - Tendeiro, Rita
AU - Foxall, Russell B.
AU - Baptista, António P.
AU - Cavaleiro, Rita
AU - Gomes, Perpétua
AU - Camacho, Ricardo
AU - Valadas, Emília
AU - Doroana, Manuela
AU - Lucas, Margarida
AU - Antunes, Francisco
AU - Victorino, Rui M.M.
AU - Sousa, Ana E.
PY - 2011/3
Y1 - 2011/3
N2 - Viremia is significantly lower in HIV-2 than in HIV-1 infection, irrespective of disease stage. Nevertheless, the comparable proviral DNA burdens observed for these two infections indicate similar numbers of infected cells. Here we investigated this apparent paradox by assessing cell-associated viral replication. We found that untreated HIV-1-positive (HIV-1+) and HIV-2+ individuals, matched for CD4 T cell depletion, exhibited similar gag mRNA levels, indicating that significant viral transcription is occurring in untreated HIV-2+ patients, despite the reduced viremia (undetectable to 2.6 × 104 RNA copies/ml). However, tat mRNA transcripts were observed at significantly lower levels in HIV-2+ patients, suggesting that the rate of de novo infection is decreased in these patients. Our data also reveal a direct relationship of gag and tat transcripts with CD4 and CD8 T cell activation, respectively. Antiretroviral therapy (ART)-treated HIV-2+ patients showed persistent viral replication, irrespective of plasma viremia, possibly contributing to the emergence of drug resistance mutations, persistent hyperimmune activation, and poor CD4 T cell recovery that we observed with these individuals. In conclusion, we provide here evidence of significant ongoing viral replication in HIV-2+ patients, further emphasizing the dichotomy between amount of plasma virus and cell-associated viral burden and stressing the need for antiretroviral trials and the definition of therapeutic guidelines for HIV-2 infection.
AB - Viremia is significantly lower in HIV-2 than in HIV-1 infection, irrespective of disease stage. Nevertheless, the comparable proviral DNA burdens observed for these two infections indicate similar numbers of infected cells. Here we investigated this apparent paradox by assessing cell-associated viral replication. We found that untreated HIV-1-positive (HIV-1+) and HIV-2+ individuals, matched for CD4 T cell depletion, exhibited similar gag mRNA levels, indicating that significant viral transcription is occurring in untreated HIV-2+ patients, despite the reduced viremia (undetectable to 2.6 × 104 RNA copies/ml). However, tat mRNA transcripts were observed at significantly lower levels in HIV-2+ patients, suggesting that the rate of de novo infection is decreased in these patients. Our data also reveal a direct relationship of gag and tat transcripts with CD4 and CD8 T cell activation, respectively. Antiretroviral therapy (ART)-treated HIV-2+ patients showed persistent viral replication, irrespective of plasma viremia, possibly contributing to the emergence of drug resistance mutations, persistent hyperimmune activation, and poor CD4 T cell recovery that we observed with these individuals. In conclusion, we provide here evidence of significant ongoing viral replication in HIV-2+ patients, further emphasizing the dichotomy between amount of plasma virus and cell-associated viral burden and stressing the need for antiretroviral trials and the definition of therapeutic guidelines for HIV-2 infection.
UR - http://www.scopus.com/inward/record.url?scp=79551712331&partnerID=8YFLogxK
U2 - 10.1128/JVI.01921-10
DO - 10.1128/JVI.01921-10
M3 - Article
C2 - 21159859
AN - SCOPUS:79551712331
SN - 0022-538X
VL - 85
SP - 2429
EP - 2438
JO - Journal of Virology
JF - Journal of Virology
IS - 5
ER -
