Deep lung – Cellular reaction to HIV

Maria Alcide Tavares Marques¹

Vera Alves²

Victor Duque³

M Filomena Botelho⁴

Resumo

A evolução da infecção VIH é caracterizada por uma grande variabilidade individual. Na verdade, omo em outros processos da mesma natureza, depende largamente das complexas inter-relacções que num dado momento se estabelecem entre o hospedeiro e o agente agressor. Contudo, nesta infecção, essa correlação assume um papel determinante.

Cedo se constatou que esta infecção se acompanhava de uma disfunção imunológica progressiva que culminava na completa exaustão deste sistema nas fases terminais da doença. Desde o reconhecimento da SIDA até à presente data foram sendo adquiridos enormes conhecimentos não só em relação ao vírus, como aos seus mecanismos patogénicos, no entanto subsistem ainda numerosas questões para as quais o estado da arte ainda não dispõe de respostas. Nessas incluíriamos os efeitos do VIH na dinâmica celular do pulmão. Vários estudos efectuados, nos quais tivemos oportunidade de participar, demonstraram a apresença de uma alveolite linfocitária durante a fase assintomática da infecção. Desde essa altura têm-se vindo a adquirir novos conhecimentos relativos aos mecanismos imunológicos e bioquímicos subjacentes à entrada do VIH nas células, às células-alvo, ao microambiente citocínico, assim como de outros mediadores celulares envolvidos. Neste contexto, a descoberta de que receptores específicos de quimiocinas actuavam como co-receptores para o VIH abriu definitivamente um novo capítulo na investigação dirigida aos mecanismos responsáveis pelo tropismo viral e infecção celular. Neste âmbito, vários autores têm salientado a importância, para além da molécula CD4, dos receptores quimiocínicos CCR5 e CXCR4 na ligação e, posteriormente, na entrada do vírus nas células, reconhecendo-se em relação ao primeiro uma importância fundamental na transmissão da infecção, enquanto que o CXCR4 parece ser utilizado por estirpes virais que emergem tardiamente no decurso da doença, quer isoladamente, quer em associação com o CCR5.

Palavras-chave: Lavagem broncoalveolar, SIDA, celularidade, receptores CCR5 e CXCR4.

Abstract

The course of HIV infection is accompanied by a wide individual variability. The complex and large interplay between host and viral factors is crucial in the disease’s evolution. The lung has been recognised from the beginning of the disease as one of the main targets of infectious and non-infectious complications of AIDS. In this setting both anatomic and immunologic particularities of this organ play an important role.

The hallmark of HIV is progressive immune dysfunction. Despite the intensive research into the pathogenesis, several questions remain to be answered on the dynamic effects of HIV on pulmonary cells. Previous studies in which we have participated showed the early presence of lymphocytic alveolitis from the asymptomatic phase of infection. Since then, many collected data has brought new insights into the immune and biochemical mechanisms involving HIV cell entry, as well as target cells, cytokines and other cellular mediators.

In this context, the discovery that specific chemokine receptors could act as co-receptors for HIV, allowed a better understanding of the mechanisms underlying viral cellular entry and tropism. On this issue several authors have reported that in addition to the CD4 molecule, most strains of HIV use the chemokine receptor CCR5 for viral attachment and entry into the host cells. This receptor seems to be very important in disease transmission, whereas CXCR4 receptor tends to be used by the viral strains that emerge later in the disease in addition to or instead of the CCR5.

Key-words: Bronchoalveolar lavage, AIDS, cellularity, CCR5 and CXCR4 receptors.

Full text only available in PDF format.

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² Instituto de Imunologia da Faculdade de Medicina de Coimbra (Director: Prof. Doutor Santos Rosa)

³ Departamento de Doenças Infecciosas dos Hospitais da Universidade de Coimbra (Director: Prof. Doutor Meliço Silvestre)

⁴ Instituto de Biofísica/Biomatemática da Faculdade de Medicina de Coimbra(Directora: Prof.ª Doutora M Filomena Botelho)

Recebido para publicação/received for publication: 06.12.10

Aceite para publicação/accepted for publication: 06.12.19