Long‐Term Intrapatient Viral Evolution during HIV‐2 Infection

The objective of this study was to estimate and compare the evolutionary rates of HIV-2 and HIV-1. Two HIV-2 data sets from patients with advanced disease were compared to matched HIV-1 data sets. The estimated mean evolutionary rate of HIV-2 was significantly higher than the estimated rate of HIV-1, both in the gp125 and in the V3 region of the env gene. In addition, the rate of synonymous substitutions in gp125 was significantly higher for HIV-2 than for HIV-1, possibly indicating a shorter generation time or higher mutation rate of HIV-2. Thus, the lower virulence of HIV-2 does not appear to translate into a lower rate of evolution.

Section: ϫ3contrasting

confidence: 99%

mentioning

confidence: 93%

mentioning

confidence: 99%

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HIV-2 Genetic Evolution in Patients with Advanced Disease Is Faster than That in Matched HIV-1 Patients

Skar

Borrego²,

Wallstrom

et al. 2010

“…In a recent report from our lab, we prospectively examined viral evolution over a decade of infection among eight HIV-2-infected individuals and observed significantly lower rates of viral evolution for HIV-2 than for HIV-1 (26), which also supports the notion that HIV-2 replication is attenuated in vivo in comparison to HIV-1 replication. It should be noted that the results of the current study do not exclude the possibility that differences in adaptive immune responses may also contribute to the lower plasma viral loads observed with HIV-2 infection.…”

Section: Discussionsupporting

confidence: 59%

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

MacNeil

Sarr

Sankalé

et al. 2007

Self Cite

Studies have shown that human immunodeficiency virus type 2 (HIV-2) is less pathogenic than HIV-1, with a lower rate of disease progression. Similarly, plasma viral loads are lower in HIV-2 infection, suggesting that HIV-2 replication is restricted in vivo in comparison to that of HIV-1. However, to date, in vivo studies characterizing replication intermediates in the viral life cycle of HIV-2 have been limited. In order to test the hypothesis that HIV-2 has a lower replication rate in vivo than HIV-1 does, we quantified total viral DNA, integrated proviral DNA, cell-associated viral mRNA, and plasma viral loads in peripheral blood samples from groups of therapy-naïve HIV-1-infected (n ‫؍‬ 21) and HIV-2-infected (n ‫؍‬ 18) individuals from Dakar, Senegal, with CD4؉ T-cell counts of >200/l. Consistent with our previous findings, total viral DNA loads were similar between HIV-1 and HIV-2 and plasma viral loads were higher among HIV-1-infected individuals. Proportions of DNA in the integrated form were also similar between these viruses. In contrast, levels of viral mRNA were lower in HIV-2 infection. Our study indicates that HIV-2 is able to establish a stable, integrated proviral infection in vivo, but that accumulation of viral mRNA is attenuated in HIV-2 infection relative to that in HIV-1 infection. The differences in viral mRNA are consistent with the differences in plasma viral loads between HIV-1 and HIV-2 and suggest that lower plasma viral loads, and possibly the attenuated pathogenesis of HIV-2, can be explained by lower rates of viral replication in vivo.

“…HIV-2 is a robust immunogen in natural infection, and patients readily make high-titer, broadly reactive, and strongly neutralizing antibodies against primary strains, something rarely seen in HIV-1 infections (1-3). In addition, HIV-2 appears slower to evolve the neutralization-resistant variant strains commonly found in HIV-1 infections (3,8). The rate of mother-to-child transmission is also much lower for HIV-2 (9), and differential neutralizing activities found in patients dually infected with HIV-1 and HIV-2 suggest the presence of distinct and divergent immune responses against these related viruses (10).…”

mentioning

confidence: 99%

Structure of an HIV-2 gp120 in Complex with CD4

Davenport

West

Björkman

2016

HIV-2 is a nonpandemic form of the virus causing AIDS, and the majority of HIV-2-infected patients exhibit long-term nonprogression. The HIV-1 and HIV-2 envelope glycoproteins, the sole targets of neutralizing antibodies, share 30 to 40% identity. As a first step in understanding the reduced pathogenicity of HIV-2, we solved a 3.0-Å structure of an HIV-2 gp120 bound to the host receptor CD4, which reveals structural similarity to HIV-1 gp120 despite divergence in amino acid sequence.