Clinical Implications of Identifying Non-B Subtypes of Human Immunodeficiency Virus Type 1 Infection (original) (raw)
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AIDS Research and Human Retroviruses, 2009
The aim of this study was the development of a panel constituted by well-defined HIV-1 strains of different genetic forms, with a particular focus on isolates from acute and recent infections. Fourteen HIV-1 isolates, including four from acute and five from recent infections, were expanded in peripheral blood mononuclear cells. SI phenotype, coreceptors use, and TCID 50 =ml were determined. V3 net charge was calculated. Near full-length genomes were amplified by RT-nested PCR in four overlapping segments. Phylogenetic analyses were performed with neighbor-joining trees and bootscanning. Analysis of cysteine residues, lengths of variable regions, and potential N-linked glycosylation sites in gp120 and gp41 was performed. Viral stocks were produced. Thirteen strains were NSI=R5 and one SI=R5,X4. TCID 50 =ml ranged between 10 4.6 and 10 6. V3 net charge was < þ5 in 12 sequences and þ5 in two sequences. Near full-length HIV-1 genomes analysis identified viruses of the following genetic forms: eight subtype B, three subtype C, two CRF02_AG, and one subtype G. Cysteine residues that form the V1,V2,V3, and V4 loops were highly conserved. The number of potential N-linked glycosylation sites in gp120 and gp41 ranged between 24-29 and 4-6, respectively. Seven potential N-linked glycosylation sites in gp120 and three in gp41 were conserved. V1, V2, V4, and V5 variable regions exhibited substantial length variation. In addition, an analysis of transmitted and natural resistance to current antiretroviral drugs in these strains was performed. It is worth mentioning that the 13S mutation in the V3 sequence, associated with resistance to maraviroc, was observed in a subtype B strain that harbored resistance mutations to nucleoside reverse transcriptase inhibitors and to T20. The availability of a panel including strains from acute and recent infections should be a valuable resource for optimizing and standardizing vaccine candidate assessment. Near full-length genome characterization may be necessary for evaluating clade-specific reactivities. A lthough subtype B viruses are the most prevalent genetic subtype of HIV-1 in North America and Western Europe and were the first viral isolates in the epidemic to be characterized, the global distribution of subtypes and circulating recombinant forms reflects the complexity of the molecular epidemiology of HIV-1. In addition, the spread of different HIV-1 variants is partly related to the biological characteristics of the virus, which could be different depending on the genetic form. 1 Consequently, due to the extraordinary degree of genetic diversity of HIV-1 and the structural complexity of its envelope glycoproteins, 2 designing an effective vaccine is difficult.
The Journal of Infectious Diseases, 2000
In the United States, human immunodeficiency virus (HIV) type 1, group M, subtype B is the predominant subtype. A cross-sectional study of HIV-infected patients at the Bronx-Lebanon Hospital Center, Bronx, NY, between September 1997 and February 1998 identified 3 (1.2%) of 252 persons infected with non-B subtypes: subtypes A and F, 1 each, and 1 potential recombinant subtype B(env)/F(prt). All 3 persons were born in the United States and tested positive for HIV antibodies between 1988 and 1997 while living in the Bronx. None reported travel to other countries, receipt of blood products, or drug injection. This study is among the first to indicate probable transmission of non-B HIV-1 subtypes in the United States. The occurrence of non-B HIV-1 subtypes in long-term US residents without a history of foreign travel may have implications for the evaluation and development of antiretroviral drugs, vaccines, and tests intended for use in the United States to diagnose HIV infection and screen blood. Two main types of human immunodeficiency virus (HIV) have been characterized: type 1, the predominant HIV type worldwide, and type 2, which is still localized mainly in persons from West Africa [1]. Group M is the predominant group of HIV-1 and consists of 10 subtypes (A-J) based on genetic characterization of envelope regions. Groups O and N are less common. To date, most HIV isolates identified in North American residents are HIV-1, group M, subtype B, and most US residents infected with non-B subtypes acquired their infections abroad [2-5]. Indigenous transmission of non-B subtypes may
Aids Research and Human Retroviruses, 2000
), and sexual partners of infected individuals. In this report, a total of 236 HIV-1-positive blood samples were collected from PBD, IDU, and their sexual partners in the most severely affected provinces, such as Henan, Yunnan, Guangxi, and Xinjiang. PCR was used to amplify the p17 region of gag and the C2-V3 region of env of HIV-1 and the 5 noncoding region and a region of E1/E2 of HCV. Genetic characterization of viral sequences indicated that there are two major epidemics of HIV-1 and multiple HCV epidemics in China. The PBD and transfusion recipients in Henan harbored HIV-1 subtype B, which is similar to the virus found in Thailand, and HCV genotypes 1b and 2a, whereas the IDU in Yunnan, Guangxi, and Xinjiang carried HIV-1 circulating recombinant forms 07 and 08, which resemble those in India, and HCV genotypes 1b, 3a, and 3b. Our findings show that the epidemics of HIV-1 and HCV infection in China are the consequences of multiple introductions. The distinct distribution patterns of both the HIV-1 and HCV genotypes in the different high-risk groups are tightly linked to the mode of transmission rather than geographic proximity. These findings provide information relevant to antiviral therapy and vaccine development in China and should assist public health workers in implementing measures to reduce the further dissemination of these viruses in the world's most populous nation.
Journal of Virology, 1998
Full-length reference clones and sequences are currently available for eight human immunodeficiency virus type 1 (HIV-1) group M subtypes (A through H), but none have been reported for subtypes I and J, which have only been identified in a few individuals. Phylogenetic information for subtype I, in particular, is limited since only about 400 bp of env gene sequences have been determined for just two epidemiologically linked viruses infecting a couple who were heterosexual intravenous drug users from Cyprus. To characterize subtype I in greater detail, we employed long-range PCR to clone a full-length provirus (94CY032.3) from an isolate obtained from one of the individuals originally reported to be infected with this subtype. Phylogenetic analysis of C2-V3 env gene sequences confirmed that 94CY032.3 was closely related to sequences previously classified as subtype I. However, analysis of the remainder of its genome revealed various regions in which 94CY032.3 was significantly cluste...
AIDS Research and Human Retroviruses, 2002
The high genetic heterogeneity of HIV-1 in the Democratic Republic of Congo (DRC) constitutes a real challenge for the development of vaccines to counter the spread of the HIV-1 epidemic. It is important to continue to monitor the epidemic by studying the circulating strains and their impact on the overall spread. As part of the ongoing effort to study the global distribution of HIV-1 subtypes and circulating recombinant forms (CRFs), here we describe a new phylogenetic clade of HIV-1 by the analysis of two full-length sequences (83CD003 and 90CD121E12) collected from two individuals at a 7-year interval (1983 and 1990, respectively). One of the two sequences (90CD121E12) was obtained from a vertically infected, 12-month-old baby in Kimpese, rural DRC, an area with low and stable seroprevalence of HIV-1 in women attending antenatal clinics. The two sequences are genetically similar by 95% of their full genome and topologically form a distinct cluster that is equidistant from the existing subtypes (A through K) by the analysis of both the full genome and subgenomic regions. Furthermore, they share several other genetic features, including an additional pair of cysteine residues, predictive of an extra disulfide bridge, in the V4 loop of gp120. This new clade is currently rare, spreading at a slower pace than the other subtypes found in the DRC region. Pending the identification of at least one partial length sequence of the same lineage from another patient who is epidemiologically unlinked to those described here, this clade is not yet named as a subtype as per the recommendation of the nomenclature committee.
The Journal of Infectious Diseases, 1997
To determine whether US residents are infected with subtypes of human immunodeficiency virus (HIV) type 1 other than subtype B (Western), the predominant North American subtype with a unique GPGR genetic sequence in the V3 loop, viruses from 22 HIV-infected adults were serotyped and subtyped. Twenty patients had subtype B (Western), of whom 15 had serotype B (Western), 3 had serotype A/C, 1 had serotype B (Thai), and 1 had a nontypeable serotype. Two had subtype A, both serotype A/C. Both subtype A-infected patients, only 1 of whom had been outside the United States, reported sex with persons traveling abroad, suggesting possible acquisition in the United States. Because US residents are infected with non-subtype B (Western) strains, US surveillance for HIV-1 diversity is needed to elucidate subtype-specific transmission patterns and pathogenesis and to guide evaluation and development of HIV diagnostic tests and vaccines. HIV-1 gp41 transmembrane proteins (groups M and O) and one
AIDS Research and Human Retroviruses, 2005
Infections with non-B HIV-1 subtypes are rare in the United States, but comprise a significant percentage of infections among U.S. military personnel. Risk behavior while on overseas deployment correlates with non-B infection in this population. Extensive genetic characterization will be required to define HIV-1 diversity, and to effectively evaluate requirements for HIV-1 vaccines and other prevention strategies in this group. From 1997 to 2000, 520 recent seroconverters, identified through routine HIV-1 testing in the U.S. active military force, volunteered for a prospective study. V3 loop serology or partial genome sequencing identified 28 non-B subtype infections; 14 were studied by full genome sequencing and phylogenetic analysis. Five strains were CRF01_AE. Four of these clustered with CM240 from Thailand, and one clustered with African CRF01_AE. Four strains were CRF02_AG, prevalent in West and West Central Africa. Two strains were subtype C. One strain was a unique recombinant between CRF01_AE and subtype B, and another was a complex unique recombinant between subtype A and D. The final strain was a member of a complex circulating recombinant first identified in Senegal, CRF09_cpx, incorporating subtypes A, F, G, and an unclassified genome. This diversity of non-B subtype HIV-1 strains, encompassing three globally prevalent non-B strains and including rare or even possibly unique strains, illustrates the breadth of U.S. military exposure while deployed and sets the bar higher for breadth of cross-subtype protection to be afforded by an HIV-1 vaccine. T HE HIV-1 PANDEMIC IS GENETICALLY DIVERSE. Nine subtypes (A-D, F-H, J, and K) and 21 circulating recombinant forms (CRF) have been identified to date. 1 Detailed molecular epidemiological studies of HIV-1 have revealed that each subtype is endemic in different parts of the world. CRF01_AE, or former subtype E, is predominant in Southeast Asia where subtype B is also circulating, along with CRF15_01B and unique recombinant forms (URF) between CRF01_AE and subtype B. In South Asia, the epidemic is subtype C, and again, subtype B cocirculates. Subtypes B, C, CRF01_AE, and two CRF_BC are circulating in China. HIV-1 subtypes in Africa are highly diverse. CRF02_AG (IbNG) is epidemic in West and West Central Africa, subtypes A, C, and D are cocirculating in East Africa, and C is the most prevalent subtype in the South and Southeast of this continent. Subtypes A, B, and CRF03_AB have been identified in Eastern Europe and Central Asia. The epidemics in Australia, Western Europe, and North America are mainly subtype B, while subtype B, BF recombinants, and C are cocirculating in South America. 2,3 In the United States, the AIDS epidemic was first recognized
Journal of Clinical Microbiology, 2015
The existing data support Portugal as the western European country with the highest HIV-1 subtype diversity. However, detailed phylogenetic studies of Portuguese HIV-1 epidemics are still scarce. Thus, our main goal was to analyze the phylodynamics of a local HIV-1 infection in the Portuguese region of Minho. Molecular epidemiological analysis was applied to data from 289 HIV-1-infected individuals followed at the reference hospital of the province of Minho, Portugal, at which isolated viruses had been sequenced between 2000 and 2012. Viruses of the G (29.1%) and B (27.0%) subtypes were the most frequent, followed by recombinant forms (17.6%) and the C (14.5%), F1 (7.3%), and A1 (4.2%) subtypes. Multinomial logistic regression revealed that the odds of being infected with the A1 and F1 subtypes increased over the years compared with those with B, G, or C subtypes or recombinant viruses. As expected, polyphyletic patterns suggesting multiple and old introductions of the B and G subtypes were found. However, transmission clusters of non-B and non-G viruses among native individuals were also found, with the dates of the most recent common ancestor estimated to be in the early 2000s. Our study supports that the HIV-1 subtype diversity in the Portuguese region of Minho is high and has been increasing in a manner that is apparently driven by factors other than immigration and international travel. Infections with A1 and F1 viruses in the region of Minho are becoming established and are mainly found in sexually transmitted clusters, reinforcing the need for more efficacious control measures targeting this infection route.