A Sudden Epidemic of HIV Type 1 among Injecting Drug Users in the Former Soviet Union: Identification of Subtype A, Subtype B, and Novel<i>gag</i>A/<i>env</i>B Recombinants

281

194

New outbreaks of human immunodeficiency virus type 1 (HIV-1) among injecting drug users (IDUs) are spreading in China along heroin trafficking routes. Recently, two separate HIV-1 epidemics among IDUs were reported in Guangxi, Southern China, where partial sequencing of the env gene showed subtype C and circulating recombinant form (CRF) AE. We evaluated five virtually full-length HIV-1 genome sequences from IDUs in Guangxi to determine the genetic diversity and the presence of intersubtype recombinants. Sequence analysis showed two geographically separated, highly homogeneous HIV-1 strains. B/C intersubtype recombinants were found in three IDUs from Baise City, in a mountainous region near the Yunnan-Guangxi border. These were mostly subtype C, with portions of the capsid and reverse transcriptase (RT) genes from subtype B. The subtype B portion of the capsid was located in the N-terminal domain, which has been shown to influence virus core maturation, virus infectivity, and binding to cyclophilin A, whereas the subtype B portion of RT was located in the palm subdomain, which is the active site of the enzyme. These BC recombinants differed from a BC recombinant found in Xinjiang Province in northwestern China. CRF AE strains were found in IDUs from Nanning, the capital of Guangxi, and in IDUs from Pingxiang City near the China-Vietnam border. The AE and BC recombinants were both remarkable for their low interpatient diversity, less than 1% for the full genome. Rapid spread of HIV-1 among IDUs may foster the emergence of highly homogeneous strains, including novel recombinants in regions with multiple subtypes.

Section: Discussionmentioning

confidence: 99%

A Recent Outbreak of Human Immunodeficiency Virus Type 1 Infection in Southern China Was Initiated by Two Highly Homogeneous, Geographically Separated Strains, Circulating Recombinant Form AE and a Novel BC Recombinant

Piyasirisilp¹,

McCutchan

Carr

et al. 2000

281

194

“…HIV-1 isolates are classified into groups M, N, and O based on sequence identity; the vast majority of the isolates belong to group M, which is further divided into different subtypes (44). Recombination can occur between closely related strains (15,34,47,56), between isolates from different subtypes (4,5,10,33,43,49,55), or even between different HIV-1 groups (41,51). Currently, many of the circulating strains of HIV-1 are intersubtype recombinants (9,26,45,46).…”

Section: High Rates Of Hiv-1 Recombination and Their Implicationsmentioning

confidence: 99%

High Rates of Human Immunodeficiency Virus Type 1 Recombination: Near-Random Segregation of Markers One Kilobase Apart in One Round of Viral Replication

Rhodes

Wargo

2003

126

118

One of the genetic consequences of packaging two copies of full-length viral RNA into a single retroviral virion is frequent recombination during reverse transcription. Many of the currently circulating strains of human immunodeficiency virus type 1 (HIV-1) are recombinants. Recombination can also accelerate the generation of multidrug-resistant HIV-1 and therefore presents challenges to effective antiviral therapy. In this study, we determined that HIV-1 recombination rates with markers 1.0, 1.3, and 1.9 kb apart were 42.4, 50.4, and 47.4% in one round of viral replication. Because the predicted recombination rate of two unlinked markers is 50%, we conclude that markers 1 kb apart segregated in a manner similar to that for two unlinked markers in one round of retroviral replication. These recombination rates are exceedingly high even among retroviruses. Recombination rates of markers separated by 1 kb are 4 and 4.7% in one round of spleen necrosis virus and murine leukemia virus replication, respectively. Therefore, HIV-1 recombination can be 10-fold higher than that of other retroviruses. Recombination can be observed only in the proviruses derived from heterozygous virions that contain two genotypically different RNAs. The high rates of HIV-1 recombination observed in our studies also indicate that heterozygous virions are formed efficiently during HIV-1 replication and most HIV-1 virions are capable of undergoing recombination. Our results demonstrate that recombination is an effective mechanism to break the genetic linkage between neighboring sequences, thereby reassorting the HIV-1 genome and increasing the diversity in the viral population.

“…Until 1995, countries of the FSU experienced only a few hundred cases of HIV-1 infection, most of which were associated with sexual transmissions. The first outbreaks of HIV-1 among IDUs in the FSU were reported in 1995 in southern Ukraine (48), followed by rapid spread of the virus in this risk group in the Russian Federation (3,5) and its neighboring countries Belarus and the Republic of Moldova in 1996 (41,50). In 1997, the virus had spread to the Baltic region, inducing a fast-growing epidemic among IDUs in Latvia and later Estonia (2,15,64).…”

mentioning

confidence: 99%

Unequal Evolutionary Rates in the Human Immunodeficiency Virus Type 1 (HIV-1) Pandemic: the Evolutionary Rate of HIV-1 Slows Down When the Epidemic Rate Increases

Berry

Ribeiro

Kothari

et al. 2007

HIV-1 sequences in intravenous drug user (IDU) networks are highly homogenous even after several years, while this is not observed in most sexual epidemics. To address this disparity, we examined the human immunodeficiency virus type 1 (HIV-1) evolutionary rate on the population level for IDU and heterosexual transmissions. All available HIV-1 env V3 sequences from IDU outbreaks and heterosexual epidemics with known sampling dates were collected from the Los Alamos HIV sequence database. Evolutionary rates were calculated using phylogenetic trees with a t test root optimization of dated samples. The evolutionary rate of HIV-1 subtype A1 was found to be 8.4 times lower in fast spread among IDUs in the former Soviet Union (FSU) than in slow spread among heterosexual individuals in Africa. Mixed epidemics (IDU and heterosexual) showed intermediate evolutionary rates, indicating a combination of fast-and slow-spread patterns. Hence, if transmissions occur repeatedly during the initial stage of host infection, before selective pressures of the immune system have much impact, the rate of HIV-1 evolution on the population level will decrease. Conversely, in slow spread, where HIV-1 evolves under the pressure of the immune system before a donor infects a recipient, the virus evolution at the population level will increase. Epidemiological modeling confirmed that the evolutionary rate of HIV-1 depends on the rate of spread and predicted that the HIV-1 evolutionary rate in a fast-spreading epidemic, e.g., for IDUs in the FSU, will increase as the population becomes saturated with infections and the virus starts to spread to other risk groups.The evolutionary rate of human immunodeficiency virus type 1 (HIV-1) has been shown to differ in different genes as well as in different regions of the same genes. Using molecularclock analyses, the rate of evolution of the env V3 region was estimated to be from 2.3 ϫ 10 Ϫ3 to 6.7 ϫ 10 Ϫ3 substitutions site Ϫ1 year Ϫ1 , while the rate for the whole env was estimated to be between 1.0 ϫ 10 Ϫ3 and 1.7 ϫ 10 Ϫ3 substitutions site Ϫ1 year Ϫ1 (25,26,33,54,63). Stronger diversifying pressure by the immune system on the V3 region is thought to be responsible for the higher rate, while genes, such as gag and pol, that are under less diversifying and more purifying selection pressure show lower rates (25,33,54