Direct Evidence of Lower Viral Replication Rates In Vivo in Human Immunodeficiency Virus Type 2 (HIV-2) Infection than in HIV-1 Infection

MacNeil, Adam; Sarr, Abdoulaye; Sankalé, Jean-Louis; Meloni, Seema; Mboup, Souleymane; Kanki, Phyllis J.

doi:10.1128/jvi.02625-06

Cited by 99 publications

(80 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The high levels of total HIV DNA observed were consistent with those from previous studies where unintegrated plus integrated proviral DNA were quantified (39,40). HIV-1 infection of human thymocytes was shown to be coreceptor dependent (9,12), and our data recapitulated these results.…”

Section: Discussionsupporting

confidence: 82%

Thymic HIV-2 Infection Uncovers Posttranscriptional Control of Viral Replication in Human Thymocytes

Nunes‐Cabaço

Matoso

Foxall

et al. 2015

J Virol

View full text Add to dashboard Cite

A unique HIV-host equilibrium exists in untreated HIV-2-infected individuals. This equilibrium is characterized by low to undetectable levels of viremia throughout the disease course, despite the establishment of disseminated HIV-2 reservoirs at levels comparable to those observed in untreated HIV-1 infection. Although the clinical spectrum is similar in the two infections, HIV-2 infection is associated with a much lower rate of CD4 T-cell decline and has a limited impact on the mortality of infected adults. Here we investigated HIV-2 infection of the human thymus, the primary organ for T-cell production. Human thymic tissue and suspensions of total or purified CD4 single-positive thymocytes were infected with HIV-2 or HIV-1 primary isolates using either CCR5 or CXCR4 coreceptors. We found that HIV-2 infected both thymic organ cultures and thymocyte suspensions, as attested to by the total HIV DNA and cell-associated viral mRNA levels. Nevertheless, thymocytes featured reduced levels of intracellular Gag viral protein, irrespective of HIV-2 coreceptor tropism and cell differentiation stage, in agreement with the low viral load in culture supernatants. Our data show that HIV-2 is able to infect the human thymus, but the HIV-2 replication cycle in thymocytes is impaired, providing a new model to identify therapeutic targets for viral replication control. IMPORTANCE HIV-1 infects the thymus, leading to a decrease in CD4 T-cell production that contributes to the characteristic CD4 T-cell loss.HIV-2 infection is associated with a very low rate of progression to AIDS and is therefore considered a unique naturally occurring model of attenuated HIV disease. HIV-2-infected individuals feature low to undetectable plasma viral loads, in spite of the numbers of circulating infected T cells being similar to those found in patients infected with HIV-1. We assessed, for the first time, the direct impact of HIV-2 infection on the human thymus. We show that HIV-2 is able to infect the thymus but that the HIV-2 replication cycle in thymocytes is impaired. We propose that this system will be important to devise immunotherapies that target viral production, aiding the design of future therapeutic strategies for HIV control.

show abstract

Section: Discussionsupporting

confidence: 82%

Thymic HIV-2 Infection Uncovers Posttranscriptional Control of Viral Replication in Human Thymocytes

Nunes‐Cabaço

Matoso

Foxall

et al. 2015

J Virol

View full text Add to dashboard Cite

show abstract

“…T cell counts and low or undetectable plasmatic viral levels [5,6], which is probably related to the slower replication capacity of the virus and a more efficient immune control compared to HIV-1 [5,[7][8][9][10][11]. In line with these phenomena, virus-specific CD8…”

Section: Introductionsupporting

confidence: 49%

HIV-2 A-subtype gp125C2-V3-C3 mutations and their association with CCR5 and CXCR4 tropism

et al. 2011

View full text Add to dashboard Cite

The early events of the HIV replication cycle involve the interaction between viral envelope glycoproteins and their cellular CD4-chemokine (CCR5/CXCR4) receptor complex. In this study, for the first time, the HIV-2 A-subtype gp125 C2-V3-C3 mutations and their tropism association were characterized by analyzing 149 HIV-2 sequences from the Los Alamos database. The analysis has strengthened the importance of C2-V3-C3 region as a determinant factor for co-receptor selection. Moreover, statistically significant correlations were observed between C2-V3-C3 mutations, and several correlated mutations were associated with CXCR4 and CCR5 co-receptor usage. A dendrogram showed two distinct clusters, with numerous associated mutations grouped, thus dividing CCR5-and CXCR4-tropic viruses. Fourteen X4-tropic virus mutations, all in V3 and C3 domains and forming highly significant subclusters, were found. Finally, R5 associations, two strong subclusters were observed, grouping several C2-V3-C3 mutated positions. These data indicate the possible contribution of C2-V3-C3 mutational patterns in regulating HIV-2 tropism.

show abstract

“…This apparent paradox highlights the potential contribution of quiescent latent virus to proviral load and the relevance of quantifying the ongoing viral replication. The only study, to our knowledge, addressing transcriptional activity in HIV-2-positive (HIV-2 ϩ ) patients demonstrated lower gag mRNA expression levels in HIV-2 ϩ than in HIV-1 ϩ individuals (34). However, the fact that these cohorts were not paired for disease stage is a possible confounding factor, as it is known that gag mRNA levels are increased in HIV-1 ϩ individuals with low CD4 T cell counts (22,39).…”

mentioning

confidence: 99%

Cell-Associated Viral Burden Provides Evidence of Ongoing Viral Replication in Aviremic HIV-2-Infected Patients

Soares¹,

Tendeiro

Foxall

et al. 2011

J Virol

View full text Add to dashboard Cite

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 ؋ 10 4 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.

show abstract

Direct Evidence of Lower Viral Replication Rates In Vivo in Human Immunodeficiency Virus Type 2 (HIV-2) Infection than in HIV-1 Infection

Cited by 99 publications

References 43 publications

Thymic HIV-2 Infection Uncovers Posttranscriptional Control of Viral Replication in Human Thymocytes

Thymic HIV-2 Infection Uncovers Posttranscriptional Control of Viral Replication in Human Thymocytes

HIV-2 A-subtype gp125C2-V3-C3 mutations and their association with CCR5 and CXCR4 tropism

Cell-Associated Viral Burden Provides Evidence of Ongoing Viral Replication in Aviremic HIV-2-Infected Patients

Contact Info

Product

Resources

About