Characterization of subtype A HIV-1 from Africa by full genome sequencing

et al. 2002

The human immunodeficiency virus type 1 (HIV-1) viral setpoint during the disease-free interval has been strongly associated with future risk of disease progression. An awareness of the correlation between viral setpoint and HIV-1 genetic evolution over time is important in the understanding of viral dynamics and infection. We examined genetic diversity in HIV-1 CRF02_A/G-IbNG-infected seroincident women in Dakar, Senegal; determined whether a viral setpoint kinetic pattern existed for CRF02_A/G-IbNG during the diseasefree interval; and correlated viral load level and diversity. Samples were drawn during the disease-free interval from consenting CRF02_A/G-IbNG-infected, antiretroviral therapy-naïve female commercial sex workers in Dakar, Senegal. Based on sequential plasma RNA values, low and high viral setpoint groups were established. Intrapatient diversity and divergence over time was determined from earlier and later time point DNA samples from each person. Most individuals followed the viral setpoint paradigm. For each 1|؊|log 10 copy/ml of plasma increase in viral load, intrapatient diversity increased by 1.4% (P ‫؍‬ 0.028). A greater diversification rate was observed in the high viral setpoint group than in the low viral setpoint group (P ‫؍‬ 0.01). Greater nucleotide (P ‫؍‬ 0.015) and amino acid (P ‫؍‬ 0.048) divergences and a greater nucleotide divergence rate (P ‫؍‬ 0.03) were found in the high viral setpoint group. There was no difference between the groups in the ratio of the number of nonsynonymous substitutions per nonsynonymous site to the number of synonymous substitutions per synonymous site. The greater intrapatient diversity, divergence, and diversification rates observed in the high viral setpoint group supports the notion that diversity is driven by cycles of viral replication resulting in accumulated mutations. Recognizing diversity potential based on viral load levels in individuals may inform the design of vaccines and therapies.

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confidence: 99%

Intrapatient Diversity and Its Correlation with Viral Setpoint in Human Immunodeficiency Virus Type 1 CRF02_A/G-IbNG Infection

Mani

Gilbert

et al. 2002

“…In areas where multiple subtypes cocirculate, it is estimated that intersubtype recombinant sequences (ISRs) account for between 8 and 24% of infections (23). Senegal has a high prevalence of CRF02AG infections (4,24,25,30,32) and recombination with this form of the virus could have been predicted. Given that subtype A viruses have been identified in a majority of the circulating intersubtype recombinants, as well as both intergroup (M/O) recombinants (10,20,24), it is also not surprising to find that the HIV-1 A3 viruses are involved in recombination events.…”

Section: Discussionmentioning

confidence: 99%

“…Nearly the entire genome was obtained in one continuous segment by using the nested primers MSF12b-OFMR1, for round 1, and F2nst-ofm19, for round 2, utilizing methods previously described (4,29). The amplicon was directly sequenced by using Big Dye terminators on an ABI 3100 capillary sequencer (Applied Biosystems), according to manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

“…This group of viruses is estimated to account for 27% of global HIV-1 infections, with a majority of the cases represented by the CRF02AG strains (23). HIV-1 infection in West Africa is principally due to CRF02AG (2,4,6,19,22,23,25). Recent work conducted in our laboratory revealed that a distinct group of viruses within the HIV-1A subtype radiation is also present in Senegal (30,32,35).…”

mentioning

confidence: 92%

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Distinct Human Immunodeficiency Virus Type 1 Subtype A Virus Circulating in West Africa: Sub-Subtype A3

Meloni

Kim

et al. 2004

Self Cite

Phylogenetic analyses demonstrate significant diversity in worldwide circulating strains of human immunodeficiency virus type 1 (HIV-1). Detailed studies have revealed a complex pattern of intersubtype recombinations, as well as evidence of sub-subtypes circulating in various populations. In this study, we characterized an HIV-1 strain that had previously been identified as a distinct subcluster within the subtype A radiation based on partial sequence data. These viruses were of particular interest given that we recently found that their prevalence was significantly higher in dually infected individuals compared to women who were singly infected with HIV-1. Five viruses isolated from commercial sex workers in Dakar, Senegal, were full-length PCR amplified and sequenced. Phylogenetic analyses indicated that, whereas three of these viruses were closely related and clustered overall within the HIV-1 subtype A radiation, they were distinct from previously characterized sub-subtype A1 and A2 viruses. The clustering pattern was maintained in the individual gag, pol, and env regions of the genome. Distance calculations between these viruses, which we termed A3, and other reference sub-subtype A1 and A2 viruses fell in the range of distances between previously characterized sub-subtype groups. In addition, we found evidence of two A3-containing recombinants in our cohort. These recombinants are mosaics composed of sequence from both sub-subtype A3 and CRF02AG, the major circulating recombinant form in this West African population. Based on phylogenetic analyses, we propose that the group of viruses found in the Dakar sex worker cohort, previously referred to as HIV-1 A subcluster 2, be referred to as HIV-1 sub-subtype A3.

“…In contrast, CRF02_AG contributes to a major number of new infections in West Africa and appears to be associated with rapidly spreading epidemics in West African countries (3,6,7,28,31,35,37). The underlying causes of the varied geographic distributions are most likely founder effects with other contributing factors, such as human population movements, unregulated commercial sex work, and intravenous drug use.Over the course of an 18-year prospective study monitoring a cohort of female sex workers (FSWs) in Dakar, Senegal, we found that the most prevalent circulating strain in the cohort is CRF02_AG, as seen in other parts of West Africa (2,6,7,28,31,35,37). However, recent work conducted in our lab revealed that a unique group of viruses within the human immunodeficiency virus type 1 (HIV-1) subtype A radiation is also present in the FSW study population (40,42).…”

mentioning

confidence: 99%

Molecular Epidemiology of Human Immunodeficiency Virus Type 1 Sub-Subtype A3 in Senegal from 1988 to 2001

Meloni

Hamel

et al. 2004

The global human immunodeficiency virus (HIV)epidemic is characterized by significant genetic diversity in circulating viruses. We have recently characterized a group of viruses that form a distinct sub-subtype within the subtype A radiation, which we have designated HIV type 1 (HIV-1) sub-subtype A, circulating in West Africa. A prospective study of a cohort of female sex workers (FSW) in Dakar, Senegal over an 18-year period indicated that an A3-specific sequence in the C2-V3 region of the env gene was found in 46 HIV-1-infected women. HIV-1 sub-subtype A3 appeared in the FSW population as early as 1988 and continued to be transmitted as of 2001. We also found that HIV-1 A3 is not confined to the FSW cohort in Senegal but is also circulating in the general population in Dakar. Furthermore, analyses of viral sequences from a few other West and Central African countries also demonstrated evidence of HIV-1 A3 sequence in isolates from HIV-1-infected people in Ivory Coast, Nigeria, Niger, Guinea Bissau, Benin, and Equatorial Guinea. Overall, because of the evidence of sub-subtype A3 in the general population in Senegal, as well as in a few neighboring West and Central African countries, along with the increasing incidence of infection with A3-containing viruses in the Dakar high-risk FSW population, we feel that HIV-1 sub-subtype A3 viruses are important to distinguish and monitor.Molecular surveillance has revealed significant heterogeneity in the prevalence and geographic distribution of various subtypes worldwide (5,35,36). For example, subtype B viruses account for an estimated 12.3% of cases globally, but infections with this subtype are primarily seen in the Americas, Western Europe, and Australia (35). Conversely, subtype C viruses were estimated to have caused Ͼ47% of the worldwide infections, with the highest incidence in southern African countries, Ethiopia, and India (35). As with the nonrecombinant subtypes, circulating recombinant forms (CRFs) also show founder effects and uneven geographic distributions. For example, CRF01_AE appears to be the cause of a high proportion of infections in Southeast Asia and seems to be largely confined to that area of the world with relatively little spread into other populations (35). In contrast, CRF02_AG contributes to a major number of new infections in West Africa and appears to be associated with rapidly spreading epidemics in West African countries (3,6,7,28,31,35,37). The underlying causes of the varied geographic distributions are most likely founder effects with other contributing factors, such as human population movements, unregulated commercial sex work, and intravenous drug use.Over the course of an 18-year prospective study monitoring a cohort of female sex workers (FSWs) in Dakar, Senegal, we found that the most prevalent circulating strain in the cohort is CRF02_AG, as seen in other parts of West Africa (2,6,7,28,31,35,37). However, recent work conducted in our lab revealed that a unique group of viruses within the human immunodeficiency virus type 1 (...