Rare HIV-1 Subtype J Genomes and a New H/U/CRF02_AG Recombinant Genome Suggests an Ancient Origin of HIV-1 in Angola

Abstract

Angola has an extremely diverse HIV-1 epidemic fueled in part by the frequent interchange of people with the Democratic Republic of Congo (DRC) and Republic of Congo (RC). Characterization of HIV-1 strains circulating in Angola should help to better understand the origin of HIV-1 subtypes and recombinant forms and their transmission dynamics. In this study we characterize the first near full-length HIV-1 genomic sequences from HIV-1 infected individuals from Angola. Samples were obtained in 1993 from three HIV-1 infected patients living in Cabinda, Angola. Near full-length genomic sequences were obtained from virus isolates. Maximum likelihood phylogenetic tree inference and analyses of potential recombination patterns were performed to evaluate the sequence classifications and origins. Phylogenetic and recombination analyses revealed that one virus was a pure subtype J, another mostly subtype J with a small uncertain region, and the final virus was classified as a H/U/CRF02_AG recombinant. Consistent with their epidemiological data, the subtype J sequences were more closely related to each other than to other J sequences previously published. Based on the env gene, taxa from Angola occur throughout the global subtype J phylogeny. HIV-1 subtypes J and H are present in Angola at low levels since at least 1993. Low transmission efficiency and/or high recombination potential may explain their limited epidemic success in Angola and worldwide. The high diversity of rare subtypes in Angola suggests that Angola was part of the early establishment of the HIV-1 pandemic.

Sensitive Next-Generation Sequencing Method Reveals Deep Genetic Diversity of HIV-1 in the Democratic Republic of the Congo

“…The basal clustering of NGSID 12 along with the unclassified isolate from the reference data set (GenBank accession number AF076475 ) with the main subtype K clade is indicative of possible recombination in these two isolates. NGSID 13 clustered within the subtype J branch along with the newly characterized subtype J isolates from Angola ( 8 ). NGSIDs 14 and 15 clustered within the main subtype H clade, while NGSID 16 clustered basal to the main subtype H clade.…”

“…The most prevalent subtypes are A, B, C, D, and G, while subtypes F, H, J, and K are collectively responsible for only 1% of all infections worldwide ( 6 ). Subtypes H, J, and K are primarily found in West, South, and Central Africa, and only 2 to 7 complete genomes have been reported, making them extremely rare ( 6 – 8 ; Los Alamos National Laboratory [LANL] HIV Database). A subtype L was suggested to be a new classification on the basis of two distinct HIV-1 genomes collected in the DRC in 1983 and 1990; however, a third epidemiologically unlinked case has not been reported ( 9 , 10 ).…”

A Prime-Boost Immunization Strategy with Vaccinia Virus Expressing Novel gp120 Envelope Glycoprotein from a CRF02_AG Isolate Elicits Cross-Clade Tier 2 HIV-1 Neutralizing Antibodies

“…Immunogens used in our study were mostly derived from R5 isolates from HIV-1 infected patients from Angola. We hypothesized that envelope glycoproteins from viruses from an old epidemic, such as the HIV epidemic in Angola, would be better at eliciting bNAbs against heterologous viruses as they comprise key epitopes and conformational determinants that should be conserved in the contemporaneous strains due to functional constraints [41,61,62]. Our results seem to confirm this hypothesis and provide the first demonstration that a vaccine based on envelope immunogens from HIV-1 clade CRF02_AG can generate neutralizing antibodies against highly divergent tier 2 HIV-1 isolates and pseudoviruses.…”

“…In the present study, we aimed to contribute new envelope-based immunogens derived from non-B clades for inclusion in a HIV-1 vaccine fit for old and very diverse HIV-1 epidemics such as those of Angola and other countries in Central Africa [41]. We produced a new set of recombinant Vaccinia virus vectors expressing a truncated form of gp120 from several primary isolates of HIV-1 of non-B clades mostly coming from Angola.…”

An in vitro Model to Mimic Selection of Replication-Competent HIV-1 Intersubtype Recombination in Dual or Superinfected Patients

“…In some instances, recombination following dual/superinfections can rescue lethally mutated genomes generated from the high mutation rate [6-8] or can result in rapid host adaptation, escape from the elicited immune responses, and/or facilitate resistance to antiretroviral drugs consequently leading to faster disease progression in infected individuals [4]. Thus, intersubtype recombination is a major driving force for HIV evolution and is changing the global epidemiology of HIV-1 with circulating recombinant forms (CRFs) dominating regional epidemics and a number of unique recombinant forms (URFs) reported each year [9-18]. …”