A clear and consistent genetic classification of human immunodeficiency virus-type 1 (HIV-1) strains continues to be of great utility in epidemiological tracking of the AIDS pandemic and in vaccine design. It also provides a foundation for detecting any biological differences that may have evolved

HIV-1 Nomenclature Proposal

https://www.cell.com/trends/molecular-medicine/pdf/S1471-4914(11)00210-3.pdf

The origin and diversity of the HIV-1 pandemic

Human immunodeficiency virus type 1 (HIV-1) is the causative agent of AIDS (10, 38, 105, 114). It is characterized by extensive and dynamic genetic diversity, generating variants falling into distinct molecular subtypes as well as recombinant forms; these forms display an uneven global distribution (55). This diversity has implications for our understanding of viral transmission, pathogenesis, and diagnosis and profoundly influences strategies for vaccine development.

Here we review selected aspects of the genetic diversity of HIV-1, with particular emphasis on its pathogenetic and therapeutic implications.

Human Immunodeficiency Virus Type 1 Subtype Distribution in the Worldwide Epidemic: Pathogenetic and Therapeutic Implications

The purpose of this study was to document the genetic diversity of human immunodeficiency virus type 1 (HIV-1) in the Democratic Republic of Congo (DRC; formerly Zaire). A total of 247 HIV-1-positive samples, collected during an epidemiologic survey conducted in 1997 in three regions (Kinshasa [the capital], Bwamanda [in the north], and Mbuyi-Maya [in the south]), were genetically characterized in the env V3-V5 region. All known subtypes were found to cocirculate, and for 6% of the samples the subtype could not be identified. Subtype A is predominant, with prevalences decreasing from north to south (69% in the north, 53% in the capital city, and 46% in the south). Subtype C, D, G, and H prevalences range from 7 to 9%, whereas subtype F, J, K, and CRF01-AE strains represent 2 to 4% of the samples; only one subtype B strain was identified. The highest prevalence (25%) of subtype C was in the south, and CRF01-AE was seen mainly in the north. The high intersubtype variability among the V3-V5 sequences is the most probable reason for the low (45%) efficiency of subtype A-specific PCR and HMA (heteroduplex mobility assay). Eighteen (29%) of 62 samples had discordant subtype designations between env and gag. Sequence analysis of the entire envelope from 13 samples confirmed the high degree of diversity and complexity of HIV-1 strains in the DRC; 9 had a complex recombinant structure in gp160, involving fragments of known and unknown subtypes. Interestingly, the unknown fragments from the different strains did not cluster together. Overall, the high number of HIV-1 subtypes cocirculating, the high intrasubtype diversity, and the high numbers of possible recombinant viruses as well as different unclassified strains are all in agreement with an old and mature epidemic in the DRC, suggesting that this region is the epicenter of HIV-1 group M.

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Unprecedented Degree of Human Immunodeficiency Virus Type 1 (HIV-1) Group M Genetic Diversity in the Democratic Republic of Congo Suggests that the HIV-1 Pandemic Originated in Central Africa

In the absence of direct epidemiological evidence, molecular evolutionary studies of primate lentiviruses provide the most definitive information about the origins of human immunodeficiency virus (HIV)–1 and HIV–2. Related lentiviruses have been found infecting numerous species of primates in sub–Saharan Africa. The only species naturally infected with viruses closely related to HIV–2 is the sooty mangabey ( Cercocebus atys ) from western Africa, the region where HIV–2 is known to be endemic. Similarly, the only viruses very closely related to HIV–1 have been isolated from chimpanzees ( Pan troglodytes ), and in particular those from western equatorial Africa, again coinciding with the region that appears to be the hearth of the HIV–1 pandemic. HIV–1 and HIV–2 have each arisen several times: in the case of HIV–1, the three groups (M, N and O) are the result of independent cross–species transmission events. Consistent with the phylogenetic position of a ‘fossil’ virus from 1959, molecular clock analyses using realistic models of HIV–1 sequence evolution place the last common ancestor of the M group prior to 1940, and several lines of evidence indicate that the jump from chimpanzees to humans occurred before then. Both the inferred geographical origin of HIV–1 and the timing of the cross–species transmission are inconsistent with the suggestion that oral polio vaccines, putatively contaminated with viruses from chimpanzees in eastern equatorial Africa in the late 1950s, could be responsible for the origin of acquired immune deficiency syndrome.

The origins of acquired immune deficiency syndrome viruses: where and when?

A Cameroonian patient with antibodies reacting simultaneously to human immunodeficiency virus type 1 (HIV-1) group O- and group M-specific V3-loop peptides was identified. In order to confirm that this patient was coinfected with both viruses, PCRs with O- and M-specific discriminating primers corresponding to different regions of the genome were carried out with both primary lymphocyte DNA and the corresponding viral strains isolated from three consecutive patient samples. The PCR data suggested that this patient is coinfected with a group M virus and a recombinant M/O virus. Indeed, only type M gag sequences could be amplified, while for the env region, both type M and O sequences were amplified, from plasma or from DNA extracted from primary lymphocytes. Sequence analysis of a complete recombinant genome isolated from the second sample (97CA-MP645 virus isolate) revealed two intergroup breakpoints, one in the vpr gene and the second in the long terminal repeat region around the TATA box. Comparison of the type M sequences shared by the group M and the recombinant M/O viruses showed that these sequences were closely related, with only 3% genetic distance, suggesting that the M virus was one of the parental viruses. In this report we describe for the first time a recombination event in vivo between viruses belonging to two different groups, leading to a replicative virus. Recombination between strains with such distant lineages (65% overall homology) may contribute substantially to the emergence of new HIV-1 variants. We documented that this virus replicates well and became predominant in vitro. At this time, group O viruses represent a minority of the strains responsible for the HIV-1 pandemic. If such recombinant intergroup viruses gained better fitness, inducing changes in their biological properties compared to the parental group O virus, the prevalences of group O sequences could increase rapidly. This will have important implications for diagnosis of HIV-1 infections by serological and molecular tests, as well as for antiviral treatment.

/pdf/characterization-of-a-highly-replicative-intergroup-m-o-2v01400008.pdf

Characterization of a Highly Replicative Intergroup M/O Human Immunodeficiency Virus Type 1 Recombinant Isolated from a Cameroonian Patient

We recently reported a high divergence among African subtype F strains. Three well-separated groups (F1, F2, and F3) have been shown based on the phylogenetic analysis of the p24 gag and envelope sequences with genetic distances similar to those observed for known subtypes. In this study, we characterized the near-full-length genomes of two strains from epidemiological unlinked individual belonging to each of the subgroups: F1 (96FR-MP411), F2 (95CM-MP255 and 95CM-MP257), and F3 (96CM-MP535 and 97ZR-EQTB11). Phylogenetic analysis of the near-full-length sequences and for each of the genes separately showed the same three groups, supported by high bootstrap values. Diversity plotting, BLAST subtyping, and bootstrap plotting confirmed that the divergent F strains correspond to nonrecombinant viruses. The divergence between F1 and F2 is consistently lower than that seen in any other intersubtype comparison, with the exception of subtypes B and D. Based on all the different analyses, we propose to divide subt...

Near-full-length genome sequencing of divergent African HIV type 1 subtype F viruses leads to the identification of a new HIV type 1 subtype designated K.

Ndongo Torimiro

Papers

Characterization of a Highly Replicative Intergroup M/O Human Immunodeficiency Virus Type 1 Recombinant Isolated from a Cameroonian Patient

Near-full-length genome sequencing of divergent African HIV type 1 subtype F viruses leads to the identification of a new HIV type 1 subtype designated K.