A subset of human immunodeficiency virus type 1 long-term non-progressors is characterized by the unique presence of ancestral sequences in the viral population

Abstract

A subset of human immunodeficiency virus type 1 long-term non-progressors is characterized by the unique presence of ancestral sequences in the viral population b 2 m level, and they were also associated with better use of safe-sex practices and higher presence of the HLA sB58 supertype than the modern subset. Viral dating has therefore permitted the segregation of LTNPs into two subsets that show very different virological, immunological, host and clinical-epidemiological characteristics. Moreover, whereas the modern subset displayed low levels of virus replication, the ancestral group displayed not only a very limited virus replication, often to undetectable levels, but also very slow or arrested viral evolution, maintaining the close relationship of the viral population to the transmitted virus. INTRODUCTIONThe natural history of human immunodeficiency virus type 1 (HIV-1) infection is heterogeneous because of the diverse duration of the AIDS-free period, although the median time of appearance of AIDS clinical symptoms is between 8 and 10 years after infection (Bacchetti & Moss, 1989; Hendriks et al., 1993; Muñoz et al., 1989). However, cohort studies have identified a small fraction of infected people, about 5-10 % (Buchbinder et al., 1994;Keet et al., 1994; Lefrère et al., 1997; Sheppard et al., 1993), who, despite infection for more than 10 years, remain symptomless and maintain a relatively high CD4 + cell count (>500 CD4 + cells ml 21 ) without antiviral therapy (Buchbinder et al., 1994;Keet et al., 1994;Learmont et al., 1992;Lifson et al., 1991; Sheppard et al., 1993). Different designations have been used for these patients, such as non-progressors (Lifson et al., 1991; Sheppard et al., 1993), long-term survivors (Levy, 1993), long-term asymptomatics (Keet et al., 1994) and long-term non-progressors (LTNPs) (Buchbinder et al., 1994).LTNPs have been associated with a low viral burden (Barker et al., 1998;Cao et al., 1995;Hogervorst et al., 1995;Pantaleo et al., 1995;Rinaldo et al., 1995) and a strong cellular (Barker et al., 1998;Cao et al., 1995;Harrer et al., 1996;Hogervorst et al., 1995;Klein et al., 1995;Pantaleo et al., 1995;Rinaldo et al., 1995)

Human Leukocyte Antigen B58 Supertype and Human Immunodeficiency Virus Type 1 Infection in Native Africans

“…We found no appreciable advantage of the B58 supertype as a whole on HIV/AIDS, in contrast to several previous studies (3,16,23,31). Different HIV-1 subtypes or HLA class I supertype frequencies could have accounted for the observed populationspecific effects of supertypes on viral control and immune escape (31).…”

“…Different HIV-1 subtypes or HLA class I supertype frequencies could have accounted for the observed populationspecific effects of supertypes on viral control and immune escape (31). The more likely reason, however, is that contributions of the individual component alleles of the B58s were not examined (3,16) or that their analysis was limited by the rarity of certain B58s alleles (23,31). In particular, the very low frequency of B*5802 among Caucasians (5) precluded assessment of its contribution to the protection by B58s seen in the Multicenter AIDS Cohort Study.…”

Human immunodeficiency virus type 1 long-term non-progressors: the viral, genetic and immunological basis for disease non-progression

“…In particular, HLA-B57 variantspredominantly B5701 and B5703 -strongly correlate with the control of HIV-1 infection by inducing a cross-reactive response against immunodominant Gag epitopes (Klein et al, 1998;Piacentini et al, 2009). HLA-B27 is also a wellstudied allele with respect to HIV-1 disease non-progression though the same relationship is not as statistically significant in large cohort studies (Bello et al, 2005;Klein et al, 1998). Interestingly, an analogous relationship has been found between HLA-B27 and the MHC class I allele, Mamu-B08, in terms of disease non-progression; elite control of viral load in rhesus macaque monkeys infected with SIV is correlated with their carriage of the Mamu-B08 allele (Loffredo et al, 2009).…”

Evaluation of Recombinant Influenza Virus-Simian Immunodeficiency Virus Vaccines in Macaques

“…Such viruses (i) have an existing reverse genetics system to readily generate and manipulate recombinant viruses (31,34), (ii) are effective as anti-influenza vaccines and licensed for human use (e.g., "Flumist" vaccine [9]) with ready production capability, (iii) have robust respiratory mucosal replication that should facilitate genital mucosal immunity, and (iv) can be generated with a variety of hemagglutinin (H) and neuraminidase (N) glycoproteins, potentially enabling these viruses to be administered sequentially in prime-boost combinations to limit the effect of antivector humoral immunity (34). Mouse-adapted recombinant influenza virus-HIV vectors have been studied in mice and demonstrated significant induction of cellular immunity at mucosal sites (8,27,28,44,48). However, although several native influenza viruses replicate efficiently in the respiratory tracts of Asian macaque species (10,12,52), no studies to date have examined the immunogenicity or efficacy of recombinant attenuated influenza virus-SIV vectors in macaques.…”