Evolution of the uniquely adaptable lentiviral envelope in a natural reservoir host

Demma, Linda J.; Vanderford, Thomas H.; Logsdon, JM; Feinberg, MB; Staprans, SI

doi:10.1186/1742-4690-3-19

Cited by 9 publications

(2 citation statements)

References 92 publications

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“…Analysis of env sequence by bulk PCR and cloning of env sequences isolated from chronically SIV-infected macaques has revealed evidence for positive selection, specifically in the V1 and V4 loops (17,29,30). Variation in V1 and V4 was similarly observed in other SIV/macaque models of infection, including SIV mac 251 infection of rhesus macaques, SIV mne infection of pig-tailed macaques, and SIV sm infection of rhesus macaques (31)(32)(33)(34)(35)(36)(37)(38)(39), as well as in the context of natural infection in sooty mangabeys (40). More recently, an analysis of env sequence variation in an animal with a potent NAb response to the parental challenge strain, SIV mac 239, identified individual substitutions within the V1 and V4 loop that, when introduced into SIV mac 239, provided resistance to the high-titer neutralizing plasma (17).…”

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confidence: 87%

High-Resolution Sequencing of Viral Populations during Early Simian Immunodeficiency Virus Infection Reveals Evolutionary Strategies for Rapid Escape from Emerging Env-Specific Antibody Responses

Ita

Hill

Lam

et al. 2018

J Virol

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Primate lentiviruses, including the human and simian immunodeficiency viruses (HIV and SIV), produce infections marked by persistent, ongoing viral replication. This occurs despite the presence of virus-specific adaptive immune responses, including antibodies targeting the viral envelope glycoprotein (Env), and evolution of antibody-escape variants is a well-documented feature of lentiviral infection. Here, we examined the evolutionary dynamics of the SIV gene during early infection (≤29 weeks postinfection) in a cohort of four SIV251-infected rhesus macaques. We tracked evolution during acute and early infection using frequent sampling and ultradeep sequencing of viral populations, capturing a transmission bottleneck and the subsequent reestablishment of Env diversity. A majority of changes in the gp120 subunit mapped to two short clusters, one in the first variable region (V1) and one in V4, while most changes in the gp41 subunit appeared in the cytoplasmic domain. Variation in V1 was dominated by short duplications and deletions of repetitive sequence, while variation in V4 was marked by short in-frame deletions and closely overlapping substitutions. The most common substitutions in both patches did not alter viral replicative fitness when tested using a highly sensitive, deep-sequencing-based competition assay. Our results, together with the observation that very similar or identical patterns of sequence evolution also occur in different macaque species infected with related but divergent strains of SIV, suggest that resistance to early, strain-specific anti-Env antibodies is the result of temporally and mutationally predictable pathways of escape that occur during the early stages of infection. The envelope glycoprotein (Env) of primate lentiviruses mediates entry by binding to host cell receptors followed by fusion of the viral membrane with the cell membrane. The exposure of Env complexes on the surface of the virion results in targeting by antibodies, leading to selection for virus escape mutations. We used the SIV/rhesus macaque model to track evolution of variation in Env during acute/early infection in animals with and without antibody responses to Env, uncovering remarkable variation in animals with antibody responses within weeks of infection. Using a deep-sequencing-based fitness assay, we found substitutions associated with antibody escape had little to no effect on inherent replicative capacity. The ability to readily propagate advantageous changes that incur little to no replicative fitness costs may be a mechanism to maintain continuous replication under constant immune selection, allowing the virus to persist for months to years in the infected host.

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mentioning

confidence: 87%

High-Resolution Sequencing of Viral Populations during Early Simian Immunodeficiency Virus Infection Reveals Evolutionary Strategies for Rapid Escape from Emerging Env-Specific Antibody Responses

Ita

Hill

Lam

et al. 2018

J Virol

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“…Lentiviruses demonstrate extensive genetic evolution throughout the course of infection (52). Not surprisingly, HIV-1 evolves within the tissues of the invaded host as a viral strategy to mediate persistent infection.…”

Section: Hiv-1 Cns Evolution and Hiv-1 Env Diversity Over The Course mentioning

confidence: 99%

Envelope Gene Evolution and HIV-1 Neuropathogenesis

Vázquez-Santiago

Rivera‐Amill

2015

J Neuroinfect Dis

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In the era of combined antiretroviral therapy (cART), HIV-associated neurocognitive disorders (HAND) account for 40 to 56% of all HIV+ cases. During the acute stage of HIV-1 infection (<6 months), the virus invades and replicates within the central nervous system (CNS). Compared to peripheral tissues, the local CNS cell population expresses distinct levels of chemokine receptors, which levels exert selective pressure on the invading virus. HIV-1 envelope (env) sequences recovered from the brains and cerebrospinal fluid (CSF) of neurocognitively impaired HIV+ subjects often display higher nucleotide variability as compared to non-impaired HIV+ subjects. Specifically, env evolution provides HIV-1 with the strategies to evade host immune response, to reduce chemokine receptor dependence, to increase co-receptor binding efficiency, and to potentiate neurotoxicity. The evolution of env within the CNS leads to changes that may result in the emergence of novel isolates with neurotoxic and neurovirulent features. However, whether specific factors of HIV-1 evolution lead to the emergence of neurovirulent and neurotropic isolates remains ill-defined. HIV-1 env evolution is an ongoing phenomenon that occurs independently of neurological and neurocognitive disease severity; thus HIV env evolution may play a pivotal and reciprocal role in the etiology of HAND. Despite the use of cART, the reactivation of latent viral reservoirs represents a clinical challenge because of the replenishment of the viral pool that may subsequently lead to persistent infection. Therefore, gaining a more complete understanding of how HIV-1 env evolves over the course of the disease should be considered for the development of future therapies aimed at controlling CNS burden, diminishing persistent viremia, and eradicating viral reservoirs. Here we review the current literature on the role of HIV-1 env evolution in the setting of HAND disease progression and on the impact of cART on the dynamics of viral evolution.

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Humoral Immune Responses in SIV Infection of Sooty Mangabeys

Derdeyn¹

2014

Natural Hosts of SIV

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Evolution of the uniquely adaptable lentiviral envelope in a natural reservoir host

Cited by 9 publications

References 92 publications

High-Resolution Sequencing of Viral Populations during Early Simian Immunodeficiency Virus Infection Reveals Evolutionary Strategies for Rapid Escape from Emerging Env-Specific Antibody Responses

High-Resolution Sequencing of Viral Populations during Early Simian Immunodeficiency Virus Infection Reveals Evolutionary Strategies for Rapid Escape from Emerging Env-Specific Antibody Responses

Envelope Gene Evolution and HIV-1 Neuropathogenesis

Humoral Immune Responses in SIV Infection of Sooty Mangabeys

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