Envelope-Constrained Neutralization-Sensitive HIV-1 After Heterosexual Transmission

Derdeyn, Cynthia A.; Decker, Julie M.; Bibollet-Ruche, Frédéric; Mokili, John L.; Muldoon, Mark; Denham, Scott A.; Heil, Marintha; Kasolo, Francis; Musonda, Rosemary; Hahn, Beatrice H.; Shaw, George M.; Korber, Bette T.; Allen, Susan; Hunter, Eric

doi:10.1126/science.1093137

Cited by 535 publications

(735 citation statements)

References 30 publications

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“…The selection of NtAb-resistant variants during MTCT is in apparent contrast to the results seen with five cases of heterosexual transmission in discordant couples in which the viruses that were transmitted were among the more neutralizationsensitive variants in the index case (11). One explanation for the difference is that sexual transmission occurs in the absence of preexisting NtAb in the exposed person; thus, the fitness of a variant for transmission may be determined by other properties of the virus.…”

Section: Discussioncontrasting

confidence: 49%

“…The latter feature, represented by fewer PNGS in envelope, was also characteristic of variants transmitted heterosexually (9,11), indicating that this may be a common property of transmitted variants independent of transmission mode. However, escape from NtAb was observed in vertically transmitted variants but the oppositenamely, neutralization sensitivity-was observed in some cases of sexually transmitted variants (11) although not in others (15). It remains to be determined whether there are common characteristics of all transmitted variants, independent of viral subtype and mode of transmission, that may provide insights into the selective pressures that occur during HIV-1 transmission.…”

Section: N Smentioning

confidence: 97%

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Neutralization Escape Variants of Human Immunodeficiency Virus Type 1 Are Transmitted from Mother to Infant

Wu¹,

Parast²,

Richardson

et al. 2006

J Virol

269

247

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Maternal passive immunity typically plays a critical role in protecting infants from new infections; however, the specific contribution of neutralizing antibodies in limiting mother-to-child transmission of human immunodeficiency virus type 1 is unclear. By examining cloned envelope variants from 12 transmission pairs, we found that vertically transmitted variants were more resistant to neutralization by maternal plasma than were maternal viral variants near the time of transmission. The vertically transmitted envelope variants were poorly neutralized by monoclonal antibodies biz, 2G12, 2F5, and 4E10 individually or in combination. Despite the fact that the infant viruses were among the most neutralization resistant in the mother, they had relatively few glycosylation sites. Moreover, the transmitted variants elicited de novo neutralizing antibodies in the infants, indicating that they were not inherently difficult to neutralize. The neutralization resistance of vertically transmitted viruses is in contrast to the relative neutralization sensitivity of viruses sexually transmitted within discordant couples, suggesting that the antigenic properties of viruses that are favored for transmission may differ depending upon mode of transmission.

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Section: Discussioncontrasting

confidence: 49%

Section: N Smentioning

confidence: 97%

Neutralization Escape Variants of Human Immunodeficiency Virus Type 1 Are Transmitted from Mother to Infant

Wu¹,

Parast²,

Richardson

et al. 2006

J Virol

269

247

View full text Add to dashboard Cite

show abstract

“…Correlations between HIV-1 transmission, variable loop length and number of putative N-linked glycosylation (PNG) sites encoded in the HIV env gene have been reported in some studies (9,10,33,58,59,60) but not in others (9,32,47). In horizontal transmission, acutely infected subjects were found to have shorter variable loops and fewer PNG sites encoded in env compared to subjects with chronic HIV-1 infection for subtypes A and C, but not subtype B (10,32,34).…”

Section: Subtype C Human Immunodeficiency Virus Type 1 (Hiv-1c) Contimentioning

confidence: 93%

“…In horizontal transmission, acutely infected subjects were found to have shorter variable loops and fewer PNG sites encoded in env compared to subjects with chronic HIV-1 infection for subtypes A and C, but not subtype B (10,32,34). In vertical transmission, one study of an HIV-1 subtype CRF_AE-infected cohort found no difference in sequence length or PNG sites, while in other studies analyzing multiple subtypes there were fewer PNG sites in transmitted viruses (47,59).…”

Section: Subtype C Human Immunodeficiency Virus Type 1 (Hiv-1c) Contimentioning

confidence: 99%

“…Studies of natural MCTC have yielded conflicting results (2,3,7,20,26,31,32,48), although possibly for identifiable reasons. The breadth of the neutralizing antibody response may depend on the subtype of HIV-1 being studied (5,10), and neutralizing antibody levels may be associated with the timing of transmission (3). A comprehensive picture of the effect of neutralizing antibodies on MTCT is difficult to obtain because of small sample sizes and different subtypes and methods involved in the reports.…”

Section: Subtype C Human Immunodeficiency Virus Type 1 (Hiv-1c) Contimentioning

confidence: 99%

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The Genetic Bottleneck in Vertical Transmission of Subtype C HIV-1 Is Not Driven by Selection of Especially Neutralization-Resistant Virus from the Maternal Viral Population

Russell¹,

Kwiek

Keys

et al. 2011

J Virol

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Subtype C human immunodeficiency virus type 1 (HIV-1C) continues to cause the majority of new cases of mother-to-child transmission (MTCT), and yet there are limited data on HIV-1C transmission. We amplified env from plasma RNA for 19 HIV-1C MTCT pairs, 10 transmitting in utero (IU) and 9 transmitting intrapartum (IP). There was a strong genetic bottleneck between all mother-infant pairs, with a majority of transmission events involving the transmission of a single virus. env genes of viruses transmitted to infants IP, but not IU, encoded Env proteins that were shorter and had fewer putative N-linked glycosylation sites in the V1-V5 region than matched maternal sequences. Viruses pseudotyped with env clones representative of each maternal and infant population were tested for neutralization sensitivity. The 50% inhibitory concentration of autologous serum was similar against both transmitted (infant) and nontransmitted (maternal) viruses in a paired analysis. Mother and infant Env proteins were also similar in sensitivity to soluble CD4, to a panel of monoclonal antibodies, and to heterologous HIV-1C sera. In addition, there was no difference in the breadth or potency of neutralizing antibodies between sera from 50 nontransmitting and 23 IU and 23 IP transmitting HIV-1C-infected women against four Env proteins from heterologous viruses. Thus, while a strong genetic bottleneck was detected during MCTC, with viruses of shorter and fewer glycosylation sites in env present in IP transmission, our data do not support this bottleneck being driven by selective resistance to antibodies.

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Nonhuman Primate Models for HIV/AIDS Vaccine Development

et al. 2013

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The development of HIV vaccines has been hampered by the lack of an animal model that can accurately predict vaccine efficacy. Chimpanzees can be infected with HIV-1 but are not practical for research. However, several species of macaques are susceptible to the Simian Immunodeficiency Viruses (SIV) that causes a disease in macaques that closely mimics HIV in humans. Thus, macaque-SIV models of HIV infection have become a critical foundation for AIDS vaccine development. Here, we examine the multiple variables and considerations that must be taken into account to use this NHP model effectively. These include the species and subspecies of macaques, virus strain, dose and route of administration and macaque genetics including Major Histocompatibility Complex molecules that affect immune responses and other virus restriction factors. We illustrate how these NHP models can be used to carry out studies of immune responses in mucosal and other tissues than could not easily be performed on human volunteers. Futhermore macaques are an ideal model system to optimize adjuvants, test vaccine platforms, and identify correlates of protection that can advance the HIV vaccine field. We also illustrate techniques used to identify different macaque lymphocyte populations and review some poxvirus vaccine candidates that are in various stages of clinical trials. Understanding how to effectively use this valuable model will greatly increase the likelihood of finding a successful vaccine for HIV.

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Envelope-Constrained Neutralization-Sensitive HIV-1 After Heterosexual Transmission

Cited by 535 publications

References 30 publications

Neutralization Escape Variants of Human Immunodeficiency Virus Type 1 Are Transmitted from Mother to Infant

Neutralization Escape Variants of Human Immunodeficiency Virus Type 1 Are Transmitted from Mother to Infant

The Genetic Bottleneck in Vertical Transmission of Subtype C HIV-1 Is Not Driven by Selection of Especially Neutralization-Resistant Virus from the Maternal Viral Population

Nonhuman Primate Models for HIV/AIDS Vaccine Development

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