title: Direct evidence of lower viral replication rates in vivo in human immunodeficiency virus type 2 (HIV-2) infection than in HIV-1 infection.
abstract: 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/microl. 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.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Ave., Boston, MA 02115, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: MacNeil
authors.forename: Abdoulaye Dieng
authors.initials: AD
authors.lastname: Sarr
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Sankalé
authors.forename: Seema Thakore
authors.initials: ST
authors.lastname: Meloni
authors.forename: Souleymane
authors.initials: S
authors.lastname: Mboup
authors.forename: Phyllis
authors.initials: P
authors.lastname: Kanki
mesh_terms: D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D015498:HIV-2 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D010949:Plasma / Q000821:virology; D011533:Proviruses / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis; D012675:Senegal; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral